The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
The formation and development of blood cells outside the BONE MARROW, as in the SPLEEN; LIVER; or LYMPH NODES.
Progenitor cells from which all blood cells derive.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
The blood-making organs and tissues, principally the bone marrow and lymph nodes.
The first of four extra-embryonic membranes to form during EMBRYOGENESIS. In REPTILES and BIRDS, it arises from endoderm and mesoderm to incorporate the EGG YOLK into the DIGESTIVE TRACT for nourishing the embryo. In placental MAMMALS, its nutritional function is vestigial; however, it is the source of INTESTINAL MUCOSA; BLOOD CELLS; and GERM CELLS. It is sometimes called the vitelline sac, which should not be confused with the VITELLINE MEMBRANE of the egg.
Formation of MYELOID CELLS from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via MYELOID STEM CELLS. Myelopoiesis generally refers to the production of leukocytes in blood, such as MONOCYTES and GRANULOCYTES. This process also produces precursor cells for MACROPHAGE and DENDRITIC CELLS found in the lymphoid tissue.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A transcription factor that dimerizes with the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain. Runx1 is frequently mutated in human LEUKEMIAS.
The production of red blood cells (ERYTHROCYTES). In humans, erythrocytes are produced by the YOLK SAC in the first trimester; by the liver in the second trimester; by the BONE MARROW in the third trimester and after birth. In normal individuals, the erythrocyte count in the peripheral blood remains relatively constant implying a balance between the rate of erythrocyte production and rate of destruction.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
The cells in the erythroid series derived from MYELOID PROGENITOR CELLS or from the bi-potential MEGAKARYOCYTE-ERYTHROID PROGENITOR CELLS which eventually give rise to mature RED BLOOD CELLS. The erythroid progenitor cells develop in two phases: erythroid burst-forming units (BFU-E) followed by erythroid colony-forming units (CFU-E); BFU-E differentiate into CFU-E on stimulation by ERYTHROPOIETIN, and then further differentiate into ERYTHROBLASTS when stimulated by other factors.
Bipotential angio-hematopoietic stem cells that give rise to both HEMATOPOIETIC STEM CELLS and ENDOTHELIAL CELLS.
A GATA transcription factor that is specifically expressed in hematopoietic lineages and plays an important role in the CELL DIFFERENTIATION of ERYTHROID CELLS and MEGAKARYOCYTES.
An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.
Leukocytes with abundant granules in the cytoplasm. They are divided into three groups according to the staining properties of the granules: neutrophilic, eosinophilic, and basophilic. Mature granulocytes are the NEUTROPHILS; EOSINOPHILS; and BASOPHILS.
The series of cells in the red blood cell lineage at various stages of differentiation.
Stem cells derived from HEMATOPOIETIC STEM CELLS. Derived from these myeloid progenitor cells are the MEGAKARYOCYTES; ERYTHROID CELLS; MYELOID CELLS; and some DENDRITIC CELLS.
One of a pair of excretory organs (mesonephroi) which grows caudally to the first pair (PRONEPHROI) during development. Mesonephroi are the permanent kidneys in adult amphibians and fish. In higher vertebrates, proneprhoi and most of mesonephroi degenerate with the appearance of metanephroi. The remaining ducts become WOLFFIAN DUCTS.
A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).
Proteins obtained from the ZEBRAFISH. Many of the proteins in this species have been the subject of studies involving basic embryological development (EMBRYOLOGY).
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
Platelet membrane glycoprotein IIb is an integrin alpha subunit that heterodimerizes with INTEGRIN BETA3 to form PLATELET GLYCOPROTEIN GPIIB-IIIA COMPLEX. It is synthesized as a single polypeptide chain which is then postranslationally cleaved and processed into two disulfide-linked subunits of approximately 18 and 110 kDa in size.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.
Connective tissue cells of an organ found in the loose connective tissue. These are most often associated with the uterine mucosa and the ovary as well as the hematopoietic system and elsewhere.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
A multilineage cell growth factor secreted by LYMPHOCYTES; EPITHELIAL CELLS; and ASTROCYTES which stimulates clonal proliferation and differentiation of various types of blood and tissue cells.
Cellular DNA-binding proteins encoded by the myb gene (GENES, MYB). They are expressed in a wide variety of cells including thymocytes and lymphocytes, and regulate cell differentiation. Overexpression of myb is associated with autoimmune diseases and malignancies.
Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets.
An encapsulated lymphatic organ through which venous blood filters.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
The entity of a developing mammal (MAMMALS), generally from the cleavage of a ZYGOTE to the end of embryonic differentiation of basic structures. For the human embryo, this represents the first two months of intrauterine development preceding the stages of the FETUS.
Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
Conditions which cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. They all involve dysregulation of multipotent MYELOID PROGENITOR CELLS, most often caused by a mutation in the JAK2 PROTEIN TYROSINE KINASE.
Immature, nucleated ERYTHROCYTES occupying the stage of ERYTHROPOIESIS that follows formation of ERYTHROID PRECURSOR CELLS and precedes formation of RETICULOCYTES. The normal series is called normoblasts. Cells called MEGALOBLASTS are a pathologic series of erythroblasts.
A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
The process of generating thrombocytes (BLOOD PLATELETS) from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW via the MEGAKARYOCYTES. The humoral factor with thrombopoiesis-stimulating activity is designated THROMBOPOIETIN.
A non-DNA binding transcription factor that is a subunit of core binding factor. It forms heterodimeric complexes with CORE BINDING FACTOR ALPHA SUBUNITS, and regulates GENETIC TRANSCRIPTION of a variety of GENES involved primarily in CELL DIFFERENTIATION and CELL CYCLE progression.
Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the PLACENTA. The cord blood is blood contained in the umbilical vessels (UMBILICAL CORD) at the time of delivery.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The number of LEUKOCYTES and ERYTHROCYTES per unit volume in a sample of venous BLOOD. A complete blood count (CBC) also includes measurement of the HEMOGLOBIN; HEMATOCRIT; and ERYTHROCYTE INDICES.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.
Any blood or formed element especially in invertebrates.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The process of generating white blood cells (LEUKOCYTES) from the pluripotent HEMATOPOIETIC STEM CELLS of the BONE MARROW. There are two significant pathways to generate various types of leukocytes: MYELOPOIESIS, in which leukocytes in the blood are derived from MYELOID STEM CELLS, and LYMPHOPOIESIS, in which leukocytes of the lymphatic system (LYMPHOCYTES) are generated from lymphoid stem cells.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
An individual that contains cell populations derived from different zygotes.
Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.
Mice bearing mutant genes which are phenotypically expressed in the animals.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
Disorders of the blood and blood forming tissues.
The developmental entity of a fertilized egg (ZYGOTE) in animal species other than MAMMALS. For chickens, use CHICK EMBRYO.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
The parent cells that give rise to both cells of the GRANULOCYTE lineage and cells of the monocyte/macrophage lineage.
A family of transcription factors that contain two ZINC FINGER MOTIFS and bind to the DNA sequence (A/T)GATA(A/G).
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A family of transcription factors that bind to the cofactor CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. Family members contain a highly conserved DNA-binding domain known as the runt domain. They can act as both activators and repressors of expression of GENES involved in CELL DIFFERENTIATION and CELL CYCLE progression.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Established cell cultures that have the potential to propagate indefinitely.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
Enlargement of the spleen.
Cell surface receptors that are specific for THROMBOPOIETIN. They signal through interaction with JANUS KINASES such as JANUS KINASE 2.
The parent cells that give rise to both cells of the MEGAKARYOCYTE and the ERYTHROCYTE lineages.
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
A receptor-regulated smad protein that undergoes PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS. It regulates BONE MORPHOGENETIC PROTEIN signaling and is essential for PHYSIOLOGICAL ANGIOGENESIS.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in leukemia.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
Anemia characterized by larger than normal erythrocytes, increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Glycoproteins found in a subfraction of normal mammalian plasma and urine. They stimulate the proliferation of bone marrow cells in agar cultures and the formation of colonies of granulocytes and/or macrophages. The factors include INTERLEUKIN-3; (IL-3); GRANULOCYTE COLONY-STIMULATING FACTOR; (G-CSF); MACROPHAGE COLONY-STIMULATING FACTOR; (M-CSF); and GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR; (GM-CSF).
Myeloid-lymphoid leukemia protein is a transcription factor that maintains high levels of HOMEOTIC GENE expression during development. The GENE for myeloid-lymphoid leukemia protein is commonly disrupted in LEUKEMIA and combines with over 40 partner genes to form FUSION ONCOGENE PROTEINS.
Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Conditions in which the abnormalities in the peripheral blood or bone marrow represent the early manifestations of acute leukemia, but in which the changes are not of sufficient magnitude or specificity to permit a diagnosis of acute leukemia by the usual clinical criteria.
Proteins prepared by recombinant DNA technology.
The unborn young of a viviparous mammal, in the postembryonic period, after the major structures have been outlined. In humans, the unborn young from the end of the eighth week after CONCEPTION until BIRTH, as distinguished from the earlier EMBRYO, MAMMALIAN.
Red blood cell precursors, corresponding to ERYTHROBLASTS, that are larger than normal, usually resulting from a FOLIC ACID DEFICIENCY or VITAMIN B 12 DEFICIENCY.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A myeloproliferative disorder of unknown etiology, characterized by abnormal proliferation of all hematopoietic bone marrow elements and an absolute increase in red cell mass and total blood volume, associated frequently with splenomegaly, leukocytosis, and thrombocythemia. Hematopoiesis is also reactive in extramedullary sites (liver and spleen). In time myelofibrosis occurs.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.
Irradiation of the whole body with ionizing or non-ionizing radiation. It is applicable to humans or animals but not to microorganisms.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A condition characterized by the recurrence of HEMOGLOBINURIA caused by intravascular HEMOLYSIS. In cases occurring upon cold exposure (paroxysmal cold hemoglobinuria), usually after infections, there is a circulating antibody which is also a cold hemolysin. In cases occurring during or after sleep (paroxysmal nocturnal hemoglobinuria), the clonal hematopoietic stem cells exhibit a global deficiency of cell membrane proteins.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
A large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.
Genes whose loss of function or gain of function MUTATION leads to the death of the carrier prior to maturity. They may be essential genes (GENES, ESSENTIAL) required for viability, or genes which cause a block of function of an essential gene at a time when the essential gene function is required for viability.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.
In Chinese philosophy and religion, two principles, one negative, dark, and feminine (yin) and one positive, bright, and masculine (yang), from whose interaction all things are produced and all things are dissolved. As a concept the two polar elements referred originally to the shady and sunny sides of a valley or a hill but it developed into the relationship of any contrasting pair: those specified above (female-male, etc.) as well as cold-hot, wet-dry, weak-strong, etc. It is not a distinct system of thought by itself but permeates Chinese life and thought. A balance of yin and yang is essential to health. A deficiency of either principle can manifest as disease. (Encyclopedia Americana)
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Local surroundings with which cells interact by processing various chemical and physical signals, and by contributing their own effects to this environment.
A CXC chemokine that is chemotactic for T-LYMPHOCYTES and MONOCYTES. It has specificity for CXCR4 RECEPTORS. Two isoforms of CXCL12 are produced by alternative mRNA splicing.
Family of RNA viruses that infects birds and mammals and encodes the enzyme reverse transcriptase. The family contains seven genera: DELTARETROVIRUS; LENTIVIRUS; RETROVIRUSES TYPE B, MAMMALIAN; ALPHARETROVIRUS; GAMMARETROVIRUS; RETROVIRUSES TYPE D; and SPUMAVIRUS. A key feature of retrovirus biology is the synthesis of a DNA copy of the genome which is integrated into cellular DNA. After integration it is sometimes not expressed but maintained in a latent state (PROVIRUSES).
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
ANIMALS whose GENOME has been altered by GENETIC ENGINEERING, or their offspring.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Stem cells from which B-LYMPHOCYTES; T-LYMPHOCYTES; NATURAL KILLER CELLS; and some DENDRITIC CELLS derive.
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)
Lymphocyte progenitor cells that are restricted in their differentiation potential to the B lymphocyte lineage. The pro-B cell stage of B lymphocyte development precedes the pre-B cell stage.
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Early pregnancy loss during the EMBRYO, MAMMALIAN stage of development. In the human, this period comprises the second through eighth week after fertilization.
Elements of limited time intervals, contributing to particular results or situations.
The gamete-producing glands, OVARY or TESTIS.
Morphological and physiological development of EMBRYOS.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
A notch receptor that interacts with a variety of ligands and regulates SIGNAL TRANSDUCTION PATHWAYS for multiple cellular processes. It is widely expressed during EMBRYOGENESIS and is essential for EMBRYONIC DEVELOPMENT.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination.
Techniques used to add in exogenous gene sequence such as mutated genes; REPORTER GENES, to study mechanisms of gene expression; or regulatory control sequences, to study effects of temporal changes to GENE EXPRESSION.
Cell surface receptors for colony stimulating factors, local mediators, and hormones that regulate the survival, proliferation, and differentiation of hemopoietic cells.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).
Increased numbers of platelets in the peripheral blood. (Dorland, 27th ed)
A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN repeats in their cytoplasmic domains. The cytoplasmic domain of notch receptors is released upon ligand binding and translocates to the CELL NUCLEUS where it acts as transcription factor.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
The GENETIC TRANSLATION products of the fusion between an ONCOGENE and another gene. The latter may be of viral or cellular origin.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The middle germ layer of an embryo derived from three paired mesenchymal aggregates along the neural tube.
Retrovirus-associated DNA sequences (v-myb) originally isolated from the avian myeloblastosis and E26 leukemia viruses. The proto-oncogene c-myb codes for a nuclear protein involved in transcriptional regulation and appears to be essential for hematopoietic cell proliferation. The human myb gene is located at 6q22-23 on the short arm of chromosome 6. This is the point of break in translocations involved in T-cell acute lymphatic leukemia and in some ovarian cancers and melanomas. (From Ibelgaufts, Dictionary of Cytokines, 1995).
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Cells derived from a FETUS that retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
The cells in the granulocytic series that give rise to mature granulocytes (NEUTROPHILS; EOSINOPHILS; and BASOPHILS). These precursor cells include myeloblasts, promyelocytes, myelocytes and metamyelocytes.
A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Transference of cells within an individual, between individuals of the same species, or between individuals of different species.
A genus of the family RETROVIRIDAE consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Signal molecules that are involved in the control of cell growth and differentiation.
Cell surface proteins that bind cytokines and trigger intracellular changes influencing the behavior of cells.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
A leukemia affecting young children characterized by SPLENOMEGALY, enlarged lymph nodes, rashes, and hemorrhages. Traditionally classed as a myeloproliferative disease, it is now considered a mixed myeloproliferative-mylelodysplastic disorder.
A transcription factor that plays a role as a key regulator of HEMATOPOIESIS. Aberrant Ikaros expression has been associated with LYMPHOBLASTIC LEUKEMIA.
Proteins that have one or more tightly bound metal ions forming part of their structure. (Dorland, 28th ed)
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
Methods for maintaining or growing CELLS in vitro.
Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Proto-oncogenes have names of the form c-onc.
High affinity receptors for INTERLEUKIN-3. They are found on early HEMATOPOIETIC PROGENITOR CELLS; progenitors of MYELOID CELLS; EOSINOPHILS; and BASOPHILS. Interleukin-3 receptors are formed by the dimerization of the INTERLEUKIN-3 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT.
An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.
A 67-kDa sialic acid binding lectin that is specific for MYELOID CELLS and MONOCYTE-MACROPHAGE PRECURSOR CELLS. This protein is the smallest siglec subtype and contains a single immunoglobulin C2-set domain. It may play a role in intracellular signaling via its interaction with SHP-1 PROTEIN-TYROSINE PHOSPHATASE and SHP-2 PROTEIN-TYROSINE PHOSPHATASE.
A mononuclear phagocyte colony-stimulating factor (M-CSF) synthesized by mesenchymal cells. The compound stimulates the survival, proliferation, and differentiation of hematopoietic cells of the monocyte-macrophage series. M-CSF is a disulfide-bonded glycoprotein dimer with a MW of 70 kDa. It binds to a specific high affinity receptor (RECEPTOR, MACROPHAGE COLONY-STIMULATING FACTOR).
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
A receptor subunit that is a shared component of the INTERLEUKIN-3 RECEPTOR; the INTERLEUKIN-5 RECEPTOR; and the GM-CSF RECEPTOR. High affinity receptor complexes are formed with each of these receptors when their respective alpha subunits are combined with this shared beta subunit.
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.

Steroids and hematopoiesis. III. The response of granulocytic and erythroid colony-forming cells to steroids of different classes. (1/5038)

Selected androgenic and nonandrogenic steroids enhance in vitro granulocytic and erythroid colony formation by mouse marrow cells, but do so by influencing either different target cells or cells in different states of cell cycle. Etiocholanolone, a naturally occurring nonandrogenic testosterone metabolite, permits cells not in active cycle to respond to colony-stimulating factor or erythropoietin. Fluoxymesterone, a synthetic androgen, appears to enhance colony growth by increasing the responsiveness of target cells to tropic stimuli. The majority of cells responding to this androgen are in active DNA synthesis. Direct comparison, however, of etiocholanolone-dependent erythroid or granulocytic colony-forming cells demonstrates nonidentity of the target cells. Thus colony-forming units responding to different classes of steroids are in different states of cell cycle and are physically separable. The enhancement of the in vitro response of colony-forming cells to regulating hormones by steroids such as etiocholanolane suggests a mechanism by which such agents may be therapeutically effective in certain cases of marrow failure in man.  (+info)

The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. (2/5038)

Csx/Nkx2.5 is a vertebrate homeobox gene with a sequence homology to the Drosophila tinman, which is required for the dorsal mesoderm specification. Recently, heterozygous mutations of this gene were found to cause human congenital heart disease (Schott, J.-J., Benson, D. W., Basson, C. T., Pease, W., Silberbach, G. M., Moak, J. P., Maron, B. J., Seidman, C. E. and Seidman, J. G. (1998) Science 281, 108-111). To investigate the functions of Csx/Nkx2.5 in cardiac and extracardiac development in the vertebrate, we have generated and analyzed mutant mice completely null for Csx/Nkx2.5. Homozygous null embryos showed arrest of cardiac development after looping and poor development of blood vessels. Moreover, there were severe defects in vascular formation and hematopoiesis in the mutant yolk sac. Interestingly, TUNEL staining and PCNA staining showed neither enhanced apoptosis nor reduced cell proliferation in the mutant myocardium. In situ hybridization studies demonstrated that, among 20 candidate genes examined, expression of ANF, BNP, MLC2V, N-myc, MEF2C, HAND1 and Msx2 was disturbed in the mutant heart. Moreover, in the heart of adult chimeric mice generated from Csx/Nkx2.5 null ES cells, there were almost no ES cell-derived cardiac myocytes, while there were substantial contributions of Csx /Nkx2.5-deficient cells in other organs. Whole-mount &bgr;-gal staining of chimeric embryos showed that more than 20% contribution of Csx/Nkx2. 5-deficient cells in the heart arrested cardiac development. These results indicate that (1) the complete null mutation of Csx/Nkx2.5 did not abolish initial heart looping, (2) there was no enhanced apoptosis or defective cell cycle entry in Csx/Nkx2.5 null cardiac myocytes, (3) Csx/Nkx2.5 regulates expression of several essential transcription factors in the developing heart, (4) Csx/Nkx2.5 is required for later differentiation of cardiac myocytes, (5) Csx/Nkx2. 5 null cells exert dominant interfering effects on cardiac development, and (6) there were severe defects in yolk sac angiogenesis and hematopoiesis in the Csx/Nkx2.5 null embryos.  (+info)

Phenotypic and functional evidence for the expression of CXCR4 receptor during megakaryocytopoiesis. (3/5038)

The identification of stromal cell-derived factor (SDF)-1alpha as a chemoattractant for human progenitor cells suggests that this chemokine and its receptor might represent critical determinants for the homing, retention, and exit of precursor cells from hematopoietic organs. In this study, we investigated the expression profile of CXCR4 receptor and the biological activity of SDF-1alpha during megakaryocytopoiesis. CD34(+) cells from bone marrow and cord blood were purified and induced to differentiate toward the megakaryocyte lineage by a combination of stem-cell factor (SCF) and recombinant human pegylated megakaryocyte growth and development factor (PEG-rhuMGDF). After 6 days of culture, a time where mature and immature megakaryocytes were present, CD41(+) cells were immunopurified and CXCR4mRNA expression was studied. High transcript levels were detected by a RNase protection assay in cultured megakaryocytes derived from cord blood CD34(+) cells as well as in peripheral blood platelets. The transcript levels were about equivalent to that found in activated T cells. By flow cytometry, a large fraction (ranging from 30% to 100%) of CD41(+) cells showed high levels of CXCR4 antigen on their surface, its expression increasing in parallel with the CD41 antigen during megakaryocytic differentiation. CXCR4 protein was also detected on peripheral blood platelets. SDF-1alpha acts on megakaryocytes by inducing intracellular calcium mobilization and actin polymerization. In addition, in in vitro transmigration experiments, a significant proportion of megakaryocytes was observed to respond to this chemokine. This cell migration was inhibited by pertussis toxin, indicating coupling of this signal to heterotrimeric guanine nucleotide binding proteins. Although a close correlation between CD41a and CXCR4 expession was observed, cell surface markers as well as morphological criteria indicate a preferential attraction of immature megakaryocytes (low level of CD41a and CD42a), suggesting that SDF-1alpha is a potent attractant for immature megakaryocytic cells but is less active on fully mature megakaryocytes. This hypothesis was further supported by the observation that SDF-1alpha induced the migration of colony forming unit-megakaryocyte progenitors (CFU-MK) and the expression of activation-dependent P-selectin (CD62P) surface antigen on early megakaryocytes, although no effect was observed on mature megakaryocytes and platelets. These results indicate that CXCR4 is expressed by human megakaryocytes and platelets. Furthermore, based on the lower responses of mature megakaryocytes and platelets to SDF-1alpha as compared with early precursors, these data suggest a role for this chemokine in the maintenance and homing during early stages of megakaryocyte development. Moreover, because megakaryocytes are also reported to express CD4, it becomes important to reevaluate the role of direct infection of these cells by the human immunodeficiency virus (HIV)-1 in HIV-1-related thrombocytopenia.  (+info)

Organ-selective homing defines engraftment kinetics of murine hematopoietic stem cells and is compromised by Ex vivo expansion. (4/5038)

Hematopoietic reconstitution of ablated recipients requires that intravenously (IV) transplanted stem and progenitor cells "home" to organs that support their proliferation and differentiation. To examine the possible relationship between homing properties and subsequent engraftment potential, murine bone marrow (BM) cells were labeled with fluorescent PKH26 dye and injected into lethally irradiated hosts. PKH26(+) cells homing to marrow or spleen were then isolated by fluorescence-activated cell sorting and assayed for in vitro colony-forming cells (CFCs). Progenitors accumulated rapidly in the spleen, but declined to only 6% of input numbers after 24 hours. Although egress from this organ was accompanied by a simultaneous accumulation of CFCs in the BM (plateauing at 6% to 8% of input after 3 hours), spleen cells remained enriched in donor CFCs compared with marrow during this time. To determine whether this differential homing of clonogenic cells to the marrow and spleen influenced their contribution to short-term or long-term hematopoiesis in vivo, PKH26(+) cells were sorted from each organ 3 hours after transplantation and injected into lethally irradiated Ly-5 congenic mice. Cells that had homed initially to the spleen regenerated circulating leukocytes (20% of normal counts) approximately 2 weeks faster than cells that had homed to the marrow, or PKH26-labeled cells that had not been selected by a prior homing step. Both primary (17 weeks) and secondary (10 weeks) recipients of "spleen-homed" cells also contained approximately 50% higher numbers of CFCs per femur than recipients of "BM-homed" cells. To examine whether progenitor homing was altered upon ex vivo expansion, highly enriched Sca-1(+)c-kit+Lin- cells were cultured for 9 days in serum-free medium containing interleukin (IL)-6, IL-11, granulocyte colony-stimulating factor, stem cell factor, flk-2/flt3 ligand, and thrombopoietin. Expanded cells were then stained with PKH26 and assayed as above. Strikingly, CFCs generated in vitro exhibited a 10-fold reduction in homing capacity compared with fresh progenitors. These studies demonstrate that clonogenic cells with differential homing properties contribute variably to early and late hematopoiesis in vivo. The dramatic decline in the homing capacity of progenitors generated in vitro underscores critical qualitative changes that may compromise their biologic function and potential clinical utility, despite their efficient numerical expansion.  (+info)

Increase of hematopoietic responses by triple or single helical conformer of an antitumor (1-->3)-beta-D-glucan preparation, Sonifilan, in cyclophosphamide-induced leukopenic mice. (5/5038)

It has been suggested that the immunopharmacological activity of soluble (1-->3)-beta-D-glucan depends on its conformation in mice. In this study, we examined the relationship between the conformation of Sonifilan (SPG) and hematopietic responses in cyclophosphamide (Cy)-induced leukopenic mice. SPG, a high molecular weight (1-->3)-beta-D-glucan, has a triple helical conformation in water, and it was changed by treatment with aqueous sodium hydroxide to the single helical conformer (SPG-OH). The effects of SPG or SPG-OH on hematopoietic responses in cyclophosphamide induced leukopenic mice were investigated by monitoring i) gene expression of cytokines by RT-PCR, ii) protein synthesis of interleukin 6 (IL-6) by ELISA and iii) colony formation of bone marrow cells (BMC). The mice administered Cy and SPG or SPG-OH expressed and produced higher levels of IL-6 mRNA and protein than the mice administered only Cy. Gene expression of NK1.1 was also induced by Cy/SPG (or SPG-OH) treatment. Induced gene expression of stem cell factor (SCF) and macrophage-colony stimulating factor (M-CSF) by SPG/SPG-OH were also found in in vitro culture of BMC from Cy treated mice. These results strongly suggested that conformation of the glucans, single and triple helix, are independent of the hematopietic response.  (+info)

Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation. (6/5038)

The influence of antiplatelet glycoprotein (GP) antibodies on megakaryocytopoiesis in patients with idiopathic or immune thrombocytopenic purpura (ITP) has been well studied. However, the influence of GP antibodies on proplatelet formation is poorly understood. Here we investigated whether in vitro human megakaryocyte colony formation and proplatelet formation are affected by various monoclonal antiplatelet GP antibodies (MoAb). The megakaryocyte colony formation inhibition assay was performed by methylcellulose culture with modifications, using peripheral blood nonadherent mononuclear cells. The proplatelet formation inhibition assay was performed by megakaryocytes derived from CD34(+) cells, stimulated with thrombopoietin + stem cell factor, which were then incubated with antiplatelet GP MoAb for 24 or 48 hours. Anti-GP-Ibalpha MoAb (CD42b; HIP1) slightly inhibited megakaryocyte colony formation (P < .05). and strongly inhibited proplatelet formation (after 24 hours incubation, P < .0002; after 48 hours incubation, P < .0007). Anti-GP-IIb MoAb (CD41; 5B12) inhibited only proplatelet formation (only after 24 hours incubation, P <. 03). Anti-integrin alphavbeta3 MoAb (CD51/CD61; 23C6) only slightly inhibited colony size (P < .05). However, anti-GP-IIIa MoAb (CD61; Y2/51) did not inhibit either colony formation or proplatelet formation. These results suggest that antiplatelet GP MoAbs have differing effects on in vitro megakaryocyte colony formation and proplatelet formation.  (+info)

Mutant N-ras induces myeloproliferative disorders and apoptosis in bone marrow repopulated mice. (7/5038)

Mutations that activate the N-ras oncogene are among the most frequently detected genetic alterations in human acute myeloid leukemias (AMLs), Philadelphia chromosome-negative myeloproliferative disorders (MPDs), and myelodysplastic syndromes (MDSs). However, because N-ras has not been shown to induce these disorders in an in vivo model, the role of N-ras in the evolution of myeloid leukemia is unclear. To investigate the potential of N-ras to induce myeloid leukemia, lethally irradiated mice were reconstituted with bone marrow (BM) cells infected with a retroviral vector carrying activated N-ras. Approximately 60% of these mice developed hematopoietic disorders, including severe MPDs resembling human chronic myelogenous leukemia (CML) or AML with differentiation (French-American-British [FAB] classification M2). Other reconstituted mice succumbed to hematopoietic defects that were pathologically similar to human MDSs. The latter disorders appeared to be due to a myeloid impairment that was demonstrated by enumeration of day-12 colony-forming units-spleen (CFU-S) and by in vitro colony assays. A high level of apoptosis associated with thymic atrophy and peripheral blood (PB) lymphopenia was also evident in N-ras reconstituted mice. Our results are consistent with a model in which antiproliferative effects are a primary consequence of N-ras mutations and secondary transforming events are necessary for the development of myeloid leukemia. This is the first report of an in vivo model for N-ras induced MPD and leukemia.  (+info)

Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. (8/5038)

In mammals, the Rho family GTPase Rac2 is restricted in expression to hematopoietic cells, where it is coexpressed with Rac1. Rac2-deficient mice were created to define the physiological requirement for two near-identical Rac proteins in hematopoietic cells. rac2-/- neutrophils displayed significant defects in chemotaxis, in shear-dependent L-selectin-mediated capture on the endothelial substrate Glycam-1, and in both F-actin generation and p38 and, unexpectedly, p42/p44 MAP kinase activation induced by chemoattractants. Superoxide production by rac2-/- bone marrow neutrophils was significantly reduced compared to wild type, but it was normal in activated peritoneal exudate neutrophils. These defects were reflected in vivo by baseline neutrophilia, reduced inflammatory peritoneal exudate formation, and increased mortality when challenged with Aspergillus fumigatus. Rac2 is an essential regulator of multiple specialized neutrophil functions.  (+info)

Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal hematopoiesis is an increased risk of hematologic cancers, which has now been shown in several studies. However, the hematopoietic stem cells that acquire these somatic mutations also give rise to mutated immune effector cells, such as monocytes, granulocytes, and lymphocytes. These effector cells can potentially influence many disease states, especially those with a chronic inflammatory component. Indeed, several studies have now shown that clonal hematopoiesis associates with increased risk of atherosclerotic cardiovascular disease. Emerging data also associate clonal hematopoiesis to other non-hematologic diseases. Here, we will review recent studies linking clonal hematopoiesis to altered immune function, inflammation, and non-malignant diseases of aging ...
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The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. Its receptor, Flt3, is expressed on myeloid, lymphoid and dendritic cell progenitors and is considered an important growth and differentiation factor for several hematopoietic lineages. Activating mutations of Flt3 are frequently found in acute myeloid leukemia (AML) patients and associated with a poor clinical prognosis. In the present review we provide an overview of our current knowledge on the role of FL in the generation of blood cell lineages. We examine recent studies on Flt3 expression by hematopoietic stem cells and its potential instructive action at early stages of hematopoiesis. In addition, we review current findings on the role of mutated FLT3 in leukemia and the development of FLT3 inhibitors for therapeutic use to treat AML. The importance of mouse models in elucidating the role of Flt3-ligand in normal and malignant hematopoiesis is discussed.
Normal and Malignant Hematopoiesis: New Advances by Mihich, Enrico available in Trade Paperback on Powells.com, also read synopsis and reviews. An exciting glance at key issues in contemporary hematopoiesis. -The Quarterly Review of Biology
MEETING CHANGE TO VIRTUAL eSymposia: https://virtual.keystonesymposia.org/ks/live/726/page/6781 Hematopoiesis is a highly regulated and dynamic developmental process by which hematopoietic stem cells self-renew and differentiate to form all blood lineages. Disruption of hematopoiesis resulting from genetic, epigenetic, transcriptional, and/or post-translational defects or due to environmental stressors can result in benign or malignant hematologic disorders. Advances in model systems, genome-editing tools, single-cell analyses, and imaging technologies have provided insight into the molecular, cellular, and developmental basis of normal and malignant hematopoiesis. This Keystone Symposia conference brings together basic and translational researchers to discuss and debate emerging topics and recent advances on developmental hematopoiesis, adult stem cell self-renewal and stem cell niches, novel hematopoietic regulators, and the pathogenesis of bone marrow failure syndromes and leukemia. Taken ...
Isocitrate dehydrogenase 1 mutation (IDH1-R132H) was recently identified in acute myeloid leukemia with normal cytogenetics. The mutant enzyme is thought to convert α-ketoglutarate to the pathogenic 2-hydroxyglutarate (2-HG) that affects DNA methylation via inhibition of ten-eleven translocation 2. However, the role of wild-type IDH1 in normal hematopoiesis and its relevance to acute myeloid leukemia is unknown. Here we showed that zebrafish idh1 (zidh1) knockdown by morpholino and targeted mutagenesis by transcription activator-like effector nuclease might induce blockade in myeloid differentiation, as evident by an increase in pu.1 and decrease in mpo, l-plastin, and mpeg1 expression, and significantly reduce definitive hematopoiesis. Morpholino knockdown of zidh2 also induced a blockade in myeloid differentiation but definitive hematopoiesis was not affected. The hematopoietic phenotype of zidh1 knockdown was not rescuable by zidh2 messenger RNA, suggesting nonredundant functions. ...
Our study extends the understanding of the genetic predispositions underlying BCR-ABL1-negative MPNs and JAK2 V617F clonal hematopoiesis in the general population. In addition to the 46/1 JAK2 haplotype, we identify predisposition alleles associated with TERT, SH2B3, TET2, ATM, CHEK2, PINT, and GFI1B in both MPN patients and in population controls who are V617F carriers. These genes impact diverse biologic pathways such as cellular aging (TERT), JAK-STAT signaling (JAK2, SH2B3), epigenetic regulation (TET2), DNA damage repair and/or tumor suppressor function (ATM, CHEK2, PINT), and erythroid/ megakaryocyte development (GFI1B).. Age-related clonal hematopoiesis in the general population was recently found to be associated with adverse outcomes, including an increased risk of hematologic cancer and all-cause mortality.27⇓-29,37 JAK2 was among the most commonly mutated genes in these studies, which also included DNMT3A, TET2, ASXL1, and TP53. The predisposition alleles we have identified in our ...
Murine acquired immunodeficiency syndrome (MAIDS) induced by defective LP-BM5 murine leukemia virus is a disease with many similarities to human AIDS. Previous studies indicated that the depressed hematopoiesis observed in LP-BM5-infected marrow cultures may be attributable to a defect of hematopoietic stroma. We report here the generation of permanent stromal cell lines from noninfected and LP-BM5-infected marrow cultures. Retrovirus infection was confirmed by polymerase chain reaction for viral genome. The ability of these cell lines to support in vitro hematopoiesis was studied. Results indicated that, when cocultured with normal or infected nonadherent mononuclear cells, noninfected cell lines efficiently supported the production of hematopoietic precursors, whereas viral-infected cell lines induced suppression of both normal and viral-infected progenitors. Expression of cytokine genes in stromal cell lines was also examined. All cell lines expressed equivalent levels of transcripts for stem ...
phdthesis{0c477139-a4a1-40fc-a0da-8d695c46f4cb, abstract = {The possibility to manufacture hematopoietic stem cells (HSCs) in the laboratory would provide an indefinite source of cells for patients requiring bone marrow transplantation. Moreover, combined with the progress in gene editing techniques, it would provide a novel platform for gene and cell replacement therapies for a range of currently incurable congenic and acquired disorders. During my PhD, I worked with an optimized protocol for in vitro blood generation from human Pluripotent Stem Cells (hPSCs). It was designed to mimic human hematopoietic development, and allowed us to explore some aspects that could elicit in vitro generation of HSCs. Using single-cell transcriptional analysis, we could explore the gene expression dynamics driving the endothelial-to-hematopoietic transition that occurs during in vitro differentiation. We also used this platform to explore the role of adrenergic signaling in human hematopoietic development, and ...
One of the frequent manifestations of liver cirrhosis (LC) regardless of LC etiology is cytopenia, the severity of which is compounded with disease progression...
CHIP stands for Clonal Hematopoiesis of Indeterminate Significance (1-4). Up to 20% of individuals in the general population acquire mutations in their bone marrow stem cells as they age that give that population of cells a survival or clonal advantage for growth. The frequency of CHIP may be higher in patients with other cancers. CHIP increases with age, and has been shown to be a risk factor associated with cardiovascular disease and a tendency to the development of bone marrow cancers at a rate of 1% per year (1,2,5). CHIP is also associated with the development of bone marrow cancers that occur after chemotherapy. The investigators want to investigate whether CHIP is also a risk factor for chemotherapy-related complications like low blood counts, infections, cardiac events, hospitalizations, dose delays and dose reductions. They are also interested in determining if CHIP may explain why some patients do not recover normal blood counts after chemotherapy finishes.. The results from this ...
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Leukemic cells disrupt regular patterns of blood cell formation but little is understood about the mechanism. when human being CML were cultured with normal human being hematopoietic progenitor cells. Furthermore neutralization of IL-6 prevented these changes and treated the disease. Keywords: HSC CML IL-6 differentiation cytokines Intro Most hematopoietic stem cells PJ34 (HSCs) reside in the bone marrow and self-renew as necessary to maintain their figures (Mercier et al. 2012 Additionally a portion of HSCs develop into progenitor cells that become lineage-restricted and undergo considerable proliferation and differentiate to produce mature hematopoietic cells (Mayle et al. 2013 Venezia et al. 2004 Wilson et Rabbit Polyclonal to SLC38A2. al. 2008 However these normal processes are severely jeopardized with leukemia (Colmone et al. 2008 Hartwell et al. 2013 Hu et al. 2009 Krause et al. 2013 Schepers et al. 2013 While this could result from overcrowding by leukemic cells it has been shown to ...
TY - JOUR. T1 - Modulators of Hematopoiesis Disorders (a Review). AU - Salakhutdinov, N. F.. AU - Laev, S. S.. AU - Sergeevichev, D. S.. PY - 2020. Y1 - 2020. N2 - Disorders of hematopoiesis caused by the action of various factors (hemotoxic substances, drugs, cytotoxic drugs, radiation) lead to a deviation from the norm and the development of the diseases varying in complexity. The restoration of hematopoiesis under extreme conditions is vital, and the search for the drugs stimulating hematopoiesis is an extremely urgent task. The most interesting agents are low molecular weight compounds that can stimulate hematopoiesis in case of its disorders. The presented literature review discusses various factors leading to hematopoietic disorders, and drugs that have shown sufficient effectiveness in eliminating these disorders, in particular with cytostatic therapy and the treatment of hemolytic pathologies. The review can be useful in the search for agents that stimulate hematopoiesis, and is ...
Using tumor sequencing variant data, investigators identified clonal hematopoiesis mutations in blood that appear to be linked to therapy-related neoplasm risk.
This study explores the prevalence of clonal hematopoiesis related to radioactive iodine exposure and how it impacts overall survival in patients with thyroid cancer.
Structural abnormalities of the c-abl proto-oncogene are found in hematopoietic cells of more than 90 percent of individuals with chronic myelogenous leukemia. Therefore c-abl may be important in normal as well as malignant hematopoiesis. Normal human hematopoietic progenitor cells were exposed to three different c-abl sense or antisense oligodeoxynucleotides, and the effects on myeloid and erythroid colony formation were examined. The c-abl antisense oligodeoxynucleotides inhibited myeloid, but not erythroid, colony formation. The c-abl sense oligodeoxynucleotides and bcr sense and antisense oligodeoxynucleotides were not inhibitory in this assay. These data show that c-abl is critical in normal myelopoiesis and may explain the relatively selective expansion of leukocytes in patients with chronic myelogenous leukemia. ...
Link to Research profile of Professor Bo Porse Link to more information about the research conducted at the Porse Laboratory
A postdoctoral position is available in the research laboratory of Dr. Mingjiang Xu ( https://www.uthscsa.edu/academics/biomedical-sciences/faculty/profile/76546/Xu%2C-Mingjiang ) at the Department of Molecular Medicine, University of Texas Health Sa ...
Blood formation originates in a small population of hematopoietic stem cells (HSCs)1 that have been defined as pluripotent cells with self-renewal capacity ((1), (2)). The mechanisms underlying the proliferation and differentiation of HSCs are incompletely understood ((3), (4)). Both extrinsic (e.g., growth factors and cell-matrix interactions) and intrinsic factors (e.g., developmentally controlled transcription factors) are involved in the regulation of HSCs. Although hematopoietic growth factors and an adequate microenvironment are crucial for the survival and proliferation of HSCs, self-renewal/differentiation decisions in HSCs seem to be derived largely independently of cytokines and are postulated to be determined intrinsically ((4)-(8)).. Studies aimed at dissecting the molecular mechanism involved in stem cell regulation have been hampered by difficulties in obtaining populations of HSCs devoid of more differentiated progenitor cells. Apart from a paucity of distinguishing phenotypic ...
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Objectives: Phospholipase C (PLC) gamma 1 has been shown to mediate signal transduction of tyrosine kinases and affect function of hematopoietic cells. However, its role in hematopoiesis during embryonic development is currently unclear. In this study, we examined this issue using morpholino (MO) gene knockdown in zebrafish embryos. Methods: MO targeting at the exon-1-intron-1 junction of zebrafish PLC-γ1 was injected into embryos at the one- to four-cell stage (referred herein zPLC-γ1MO embryos). Primitive hematopoiesis was examined quantitatively by flow cytometry in Tg(gata1:GFP) embryos and by real-time quantitative polymerase chain reaction at 18 hours-post-fertilization (hpf), before the onset of circulation. The embryos were also treated with receptor inhibitors of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor at 25, 1, and 30 μmol/L, respectively, from one cell until 48 hpf. Results: Erythropoiesis was reduced in zPLC-γ1MO embryos, ...
Looking for hematopoiesis depression? Find out information about hematopoiesis depression. The process by which the cellular elements of the blood are formed. The three main types of cells are the red cells , which serve to carry oxygen, the white... Explanation of hematopoiesis depression
Vertebrate hematopoiesis first produces primitive (embryonic) lineages and ultimately generates the definitive (adult) blood. Whereas definitive hematopoiesis may produce many diverse blood types via a common multipotent progenitor, primitive hematopoiesis has been thought to produce only erythrocytes or macrophages via progenitors that are unipotent for single blood lineages. Using a variety of in vivo cell-tracing techniques, we show that primitive blood in zebrafish derives from two different progenitor types. On the dorsal gastrula, blood progenitors are unipotential cells that divide infrequently, populate the rostral blood islands, and differentiate into macrophages. In contrast, on the ventral gastrula, blood progenitors are multipotential cells with rapid cell cycles; populate the intermediate cell mass; and differentiate into erythrocytes, neutrophils, and thrombocytes. Our results demonstrate the existence of primitive hematopoietic progenitors that are segregated very early in ...
Wnt5a Does Not Support Hematopoiesis in Stroma-Free, Serum-Free Cultures. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
TY - JOUR. T1 - Cloning and characterization of two novel transcription factors differentially expressed during blood cell development. AU - Nachtman, Ronald G.. AU - Abdullah, James M.. AU - Jing, Xin. AU - Li, Xinyu. AU - Infante, Jorge L.. AU - Jurecic, Roland. PY - 2000/12/1. Y1 - 2000/12/1. N2 - By performing a comprehensive degenerate PCR cloning and developmental and tissuespecific expression analysis of Cys2-His2 type zinc finger (ZF) genes expressed in mouse bone marrow HSC population (LinSca-1 cells) we have identified several new ZF genes with differential expression in specific stages of blood cell development. Here we describe Vulcan and Tycho, two new ZF genes with tissue-restricted and developmentally regulated expression during hematopoiesis. Vulcan encodes a ZF protein with a novel type of KRAB A represser domain, which is expressed throughout mouse embryonic development, and in adult thymus, spleen, thyroid, submaxillary gland, brain and testis. During embryonic hematopoiesis ...
The HOX genes are a highly conserved family of homeodomain-containing transcription factors that specify cell identity in early development and, subsequently, in a number of adult processes including hematopoiesis. The dysregulation of HOX genes is associated with a number of malignancies including acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL), where they have been shown to support the immortalization of leukemic cells both as chimeric partners in fusion genes and when overexpressed in their wild type form. This review covers our current understanding of the role of HOX genes in normal hematopoiesis, AML and ALL, with particular emphasis on the similarities and differences of HOX function in these contexts, their hematopoietic downstream genes targets and implications for therapy.Leukemia accepted article preview online, 5 December 2012; doi:10.1038/leu.2012.356.. ...
During early development, the various cell types of the hematopoietic system are formed at distinct anatomical niches within the embryo, in a spatially and temporally controlled manner, until this function is completely taken over by the bone marrow and thymus (for T-lymphoid cell generation) just prior to birth. A number of studies have now confirmed that the development of the hematopoietic system, in humans and other mammals, occurs in two phases: a primitive hematopoietic phase that gives rise to transitory, bi-potent HSCs, and a definitive hematopoietic phase that generates long-lived, multipotent HSCs [3].. Primitive hematopoiesis: The primitive phase of hematopoiesis starts very early, at around the third week of mammalian embryo development, in an extraembryonic tissue called the yolk sac. Within this yolk sac, mesodermal cells start forming cell aggregates at around day 16 of embryo development [4]. Soon after, the peripheral cells of the aggregate acquire endothelial characteristics, ...
▪ biochemistry also called Hematopoiesis, or Hemopoiesis, continuous process by which the cellular constituents of blood are replenished as needed. Blood cells are divided into three groups: the red blood cells (erythrocytes (erythrocyte)),…
Polly Clayden, HIV i-Base. A report from the French Perinatal Study published in the September issue of AIDS found that perinatal exposure to zidovudine might result in a small but significant and durable effect on haematopoiesis up to the age of 18 months.. The French Perinatal Study, established in 1986, prospectively follows infected and uninfected infants born to HIV-positive mothers.. In a longitudinal study, the investigators analysed haematological variables in 4,249 infants from zero to 18 months including haemoglobin, platelets, polynuclear neutrophils, total lymphocytes, and CD4+ and CD8+ lymphocytes. To perform the analysis they used non-parametric smoothing techniques. Modeling of repeated measures and non-linear evolution with age, with models combining natural cubic B-splines and random effects.. The investigators reported a transient reduction in haemoglobin levels in newborns exposed to zidovudine. Multivariate analysis taking into account age, prematurity, geographical origin, ...
Schuler, F., Afreen, S., Manzl, C., Häcker, G., Erlacher, M.,Villunger, A. Checkpoint kinase 1 is essential for fetal and adult hematopoiesis. EMBO Reports. 2019; e47026. doi:10.15252/embr.201847026. ...
TY - JOUR. T1 - Engraftment and Reconstitution of Hematopoiesis Is Dependent on VEGFR2-Mediated Regeneration of Sinusoidal Endothelial Cells. AU - Hooper, Andrea T.. AU - Butler, Jason M.. AU - Nolan, Daniel J.. AU - Kranz, Andrea. AU - Iida, Kaoruko. AU - Kobayashi, Mariko. AU - Kopp, Hans Georg. AU - Shido, Koji. AU - Petit, Isabelle. AU - Yanger, Kilangsungla. AU - James, Daylon. AU - Witte, Larry. AU - Zhu, Zhenping. AU - Wu, Yan. AU - Pytowski, Bronislaw. AU - Rosenwaks, Zev. AU - Mittal, Vivek. AU - Sato, Thomas N.. AU - Rafii, Shahin. PY - 2009/3/6. Y1 - 2009/3/6. N2 - Myelosuppression damages the bone marrow (BM) vascular niche, but it is unclear how regeneration of bone marrow vessels contributes to engraftment of transplanted hematopoietic stem and progenitor cells (HSPCs) and restoration of hematopoiesis. We found that chemotherapy and sublethal irradiation induced minor regression of BM sinusoidal endothelial cells (SECs), while lethal irradiation induced severe regression of SECs ...
Human cyclic haematopoiesis (cyclic neutropenia, MIM 162800) is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individ …
article{c03f23fd-8614-4859-a337-573f18b13144, author = {Svensson, Emelie and Eriksson, Helena and Gekas, Christos and Olofsson, Tor and Richter, Johan and Gullberg, Urban}, issn = {1090-2422}, language = {eng}, number = {1}, pages = {211--221}, publisher = {Academic Press}, series = {Experimental Cell Research}, title = {DNA-binding dependent and independent functions of WT1 protein during human hematopoiesis.}, url = {http://dx.doi.org/10.1016/j.yexcr.2005.04.018}, doi = {10.1016/j.yexcr.2005.04.018}, volume = {308}, year = {2005 ...
Creative Animodel provides custom preclinical animal services for human hematopoiesis from model development, lead drug candidate efficacy studies, to toxicology testing.
AACR membership is available to individuals who are interested in joining the AACR and registering for this conference at the discounted member rates. AACR membership offers an array of benefits, including reduced subscriptions to the AACRs eight scientific journals; abstract sponsorship privileges for AACR Annual Meetings; networking and scientific exchange with leading researchers; and more. The AACR is also eager to support the exchange of knowledge and research with investigators who are located in countries with emerging economies. Significantly reduced membership dues are available for these investigators. Additional information on AACR membership categories, as well as application forms and submission instructions, is available on the membership section of the AACR website. Applications for membership should be submitted at least two weeks prior to the start of the conference.. ...
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TY - JOUR. T1 - In vivo modulation of hematopoiesis by a novel hematoregulatory peptide. AU - Pelus, L. M.. AU - King, A. G.. AU - Broxmeyer, H. E.. AU - DeMarsh, P. L.. AU - Peteway, S. R.. AU - Bhatnagar, P. K.. PY - 1994/3/18. Y1 - 1994/3/18. N2 - The hematoregulatory peptide dimer, HP5B, enhances myelopoiesis by stimulating stromal cell cytokine production. However, the disulfide bridge of this peptide is susceptible to reduction, leading to the formation of monomeric pentapeptide, HP5, a direct-acting inhibitor of myelopoiesis. We have replaced the disulfide (S-S)d bond of HP5B dimer with an isosteric ethylene (CH2-CH2) group, creating a new, nonreducible, metabolically more stable peptide (SK and F 107647). This novel peptide was tested in vitro and in vivo for hematopoietic effects. In vitro, SK and F 107647 has no direct colony-stimulating activity (CSA). Stimulation of murine stromal cells with SK and F 107647 results in production and release of CSA at concentrations as low as 0.01 ...
The model organism Danio rerio, also known as the zebrafish, is an excellent system for studying the developmental process of hematopoiesis. It is an ideal model for in vivo imaging, and it is useful for large-scale genetic screens. These have led to the discovery of previously unknown players in hematopoiesis, as well as helped our understanding of hematopoietic development. In this review, we will summarize hematopoiesis in the zebrafish and discuss how genetic approaches using the zebrafish system have helped to build our current knowledge in the field of hematopoiesis.
Colour enhanced scanning electron micrograph (SEM) of mouse blood, showing expulsion of nucleus from red blood cell prior to cell formation. Magnification: 22,500x when printed at 6x6. - Stock Image C022/0443
Molecular mechanisms underlying blood development and disorders are of great interest and importance from the perspective of understanding normal function and l...
The overarching themes of our 11th World Congress on Targeting Mitochondria will not significantly deviate from topics discussed at preceding editions of our conference series.
Hematopoiesis News is an online publication and email newsletter that provides updates on the latest research in the fields of hematopoiesis, blood, and bone marrow disorders.
Speaker: Dr Cristina Lo Celso, Imperial College London. Title: Healthy and malignant haematopoiesis in the bone marrow: dynamic cells in an evolving environment.
This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling. The expression of this gene is induced by various cytokines, including IL6, IL10, and interferon (IFN)-gamma. The protein encoded by this gene can bind to JAK2 kinase, and inhibit the activity of JAK2 kinase. Studies of the mouse counterpart of this gene suggested the roles of this gene in the negative regulation of fetal liver hematopoiesis, and placental development. [provided by RefSeq, Jul 2008 ...
Hematopoiesis is the process that creates blood cells. The monophyletic theory in Hematopoiesis, which is widely accepted, suggests that all hematopoietic cells are generated based on pluripotent stem cells, making them unipotential and differentiated into precursor cells before continuing to form mature blood cells. Hematopoiesis during the early stages of embryogenesis occurs in the egg yolk.... ...
Summary: Discovery of novel PAX-SIX-EYA-DACH and GATA network interactions in Drosophila hematopoiesis reveal that human SIX proteins can associate with GATA1, stimulate GATA1-dependent transcription and enhance human erythropoiesis in vitro. ...
Hematopoiesis is the process of formation of blood cellular components derived from derived from hematopoietic stem cells. These hematopoietic stem cells p..
TY - JOUR. T1 - Hepatic differentiation induced by oncostatin M attenuates fetal liver hematopoiesis. AU - Kinoshita, Taisei. AU - Sekiguchi, Takashi. AU - Xu, Ming Jiang. AU - Ito, Yoshiaki. AU - Kamiya, Akihide. AU - Tsuji, Koh Ichiro. AU - Nakahata, Tatsutoshi. AU - Miyajima, Atsushi. PY - 1999/6/22. Y1 - 1999/6/22. N2 - Embryonic liver is a transient site for definitive hematopoiesis. Along with maturation of the bone marrow and spleen, hematopoietic cells relocate from the liver to their final destinations while the liver starts organizing its own structure and develops numerous metabolic functions toward adult. Recently, it was demonstrated that the signal exerted by oncostatin M (OSM) through gp130 plays a pivotal role in the maturation process of the liver both in vitro and in vivo. However, the molecular basis underlying the termination of embryonic hematopoiesis remains unknown. In this study, we report that primary culture of fetal hepatic cells from embryonic day 14.5 murine embryos ...
Hematopoietic stem cell (HSC) niches in bone marrow have been described in terms of distinct cell types including osteoblastic, endothelial and perivascular reticular cells. However, niches which support extramedullary hematopoiesis in other sites like spleen remain to be elucidated. Previous studies have described splenic stromal cells which support hematopoiesis in vitro from purified HSC and multipotential progenitors (MPP) leading to the production of dendritic-like cells. Stromal cell lines were originally derived from splenocyte cultures, and later as freshly isolated stromal subsets prepared by enzymatic digestion and sorting. Transcriptome analysis has revealed that stroma which support hematopoiesis express many genes in parallel with perivascular cells described in bone marrow. They share a common mesenchymal lineage with perivascular cells in bone marrow, as well as mesenchymal progenitor cells and CXCL12-abundant reticular cells. They reflect osteoprogenitors in that cells can be induced to
Wnt signaling increases hematopoietic stem cell self-renewal and is activated in both myeloid and lymphoid malignancies, indicating involvement in both normal and malignant hematopoiesis. We report here activated canonical Wnt signaling in the hematopoietic system through conditional expression of a stable form of beta-catenin. This enforced expression led to hematopoietic failure associated with loss of myeloid lineage commitment at the granulocyte-macrophage progenitor stage; blocked erythrocyte differentiation; disruption of lymphoid development; and loss of repopulating stem cell activity. Loss of hematopoietic stem cell function was associated with decreased expression of Cdkn1a ( encoding the cell cycle inhibitor p21(cdk)), Sfpi1, Hoxb4 and Bmi1 ( encoding the transcription factors PU.1, HoxB4 and Bmi-1, respectively) and altered integrin expression in Lin(-)Sca-1(+)c-Kit(+) cells, whereas PU.1 was upregulated in erythroid progenitors. Constitutive activation of canonical Wnt signaling ...
Background Cdx4 is a homeobox gene essential for normal blood formation during embryonic development in the zebrafish, through activation of posterior hox genes. However, its role in adult mammalian hematopoiesis has not been extensively studied and its requirement in leukemia associated with Hox gene expression alteration is unclear. Design and Methods We inactivated Cdx4 in mice through either a germline or conditional knockout approach and analyzed requirement for Cdx4 in both normal adult hematopoiesis and leukemogenesis initiated by the MLL-AF9 fusion oncogene. Results Here, we report that loss of Cdx4 had minimal effect on adult hematopoiesis. Indeed, although an increase in white blood cell counts was observed, no significant difference in the distribution of mature blood cells, progenitors or stem cells were observed in Cdx4-deficient animals. In addition, long-term repopulating activity in competitive transplantation assays was not significantly altered. In vitro, B-cell progenitor ...
TY - JOUR. T1 - The Paf oncogene is essential for hematopoietic stem cell function and development. AU - Amrani, Yacine M.. AU - Gill, Jonathan. AU - Matevossian, Armine. AU - Alonzo, Eric S.. AU - Yang, Chingwen. AU - Shieh, Jae Hung. AU - Moore, Malcolm A.. AU - Park, Christopher Y.. AU - SantAngelo, Derek B.. AU - Denzin, Lisa K.. PY - 2011/8/29. Y1 - 2011/8/29. N2 - Hematopoietic stem cells (HSCs) self-renew to maintain the lifelong production of all blood populations. Here, we show that the proliferating cell nuclear antigen-associated factor (Paf) is highly expressed in cycling bone marrow HSCs and plays a critical role in hematopoiesis. Mice lacking Paf exhibited reduced bone marrow cellularity; reduced numbers of HSCs and committed progenitors; and leukopenia. These phenotypes are caused by a cellintrinsic blockage in the development of long-term (LT)-HSCs into multipotent progenitors and preferential loss of lymphoid progenitors caused by markedly increased p53-mediated apoptosis. In ...
Chromatin-modifying enzymes, and specifically the protein arginine methyltransferases (PRMTs), have emerged as important targets in cancer. Here, we investigated the role of CARM1 in normal and malignant hematopoiesis. Using conditional knockout mice, we show that loss of CARM1 has little effect on normal hematopoiesis. Strikingly, knockout of Carm1 abrogates both the initiation and maintenance of acute myeloid leukemia (AML) driven by oncogenic transcription factors. We show that CARM1 knockdown impairs cell-cycle progression, promotes myeloid differentiation, and ultimately induces apoptosis. Finally, we utilize a selective, small-molecule inhibitor of CARM1 to validate the efficacy of CARM1 inhibition in leukemia cells in vitro and in vivo. Collectively, this work suggests that targeting CARM1 may be an effective therapeutic strategy for AML.. Greenblatt, Sarah & Man, Na & Hamard, Pierre-Jacques & Asai, Takashi & Karl, Daniel & Martinez, Concepcion & Bilbao, Daniel & Stathais, Vasileios & ...
The current paradigm that a single long-term hematopoietic stem cell can regenerate all components of the mammalian immune system has been challenged by recent findings in mice. These findings show that adult tissue-resident macrophages and innate-like lymphocytes develop early in fetal hematopoiesis from progenitors that emerge prior to, and apparently independently of, conventional long-term hematopoietic stem cells. Here, we discuss these recent findings, which show that an early and distinct wave of hematopoiesis occurs for all major hematopoietic lineages. These data provide evidence that fetal hematopoietic progenitors not derived from the bona fide long-term hematopoietic stem cells give rise to tissue-resident immune cells that persist throughout adulthood. We also discuss recent insights into B lymphocyte development and attempt to synthesize seemingly contradictory recent findings on the origins of innate-like B-1a lymphocytes during fetal hematopoiesis ...
Mutations in genes involved in DNA methylation (DNAme; for example, TET2 and DNMT3A) are frequently observed in hematological malignancies1-3 and clonal hematopoiesis4,5. Applying single-cell sequencing to murine hematopoietic stem and progenitor cells, we observed that these mutations disrupt hematopoietic differentiation, causing opposite shifts in the frequencies of erythroid versus myelomonocytic progenitors following Tet2 or Dnmt3a loss. Notably, these shifts trace back to transcriptional priming skews in uncommitted hematopoietic stem cells. To reconcile genome-wide DNAme changes with specific erythroid versus myelomonocytic skews, we provide evidence in support of differential sensitivity of transcription factors due to biases in CpG enrichment in their binding motif. Single-cell transcriptomes with targeted genotyping showed similar skews in transcriptional priming of DNMT3A-mutated human clonal hematopoiesis bone marrow progenitors. These data show that DNAme shapes the topography of
The canonical Wnt signaling pathway plays key roles in stem-cell maintenance, progenitor cell expansion, and lineage decisions. Transcriptional responses induced by Wnt depend on the association of either beta-catenin or gamma-catenin with lymphoid enhancer factor/T cell factor transcription factors. Here we show that hematopoiesis, including thymopoiesis, is normal in the combined absence of beta- and gamma-catenin. Double-deficient hematopoietic stem cells maintain long-term repopulation capacity and multilineage differentiation potential. Unexpectedly, 2 independent ex vivo reporter gene assays show that Wnt signal transmission is maintained in double-deficient hematopoietic stem cells, thymocytes, or peripheral T cells. In contrast, Wnt signaling is strongly reduced in thymocytes lacking TCF-1 or in nonhematopoietic cells devoid of beta-catenin. These data provide the first evidence that hematopoietic cells can transduce canonical Wnt signals in the combined absence of beta- and gamma-catenin.
Marian Blanca Ramírez from the CSIC in Spain has been studying the effects of LRRK2, a protein associated with Parkinsons disease, on cell motility. A Travelling Fellowship from Journal of Cell Science allowed her to spend time in Prof Maddy Parsons lab at Kings College London, learning new cell migration assays and analysing fibroblasts cultured from individuals with Parkinsons. Read more on her story here. Where could your research take you? The deadline to apply for the current round of Travelling Fellowships is 30 Nov 2017. Apply now!. ...
Maintenance of blood homeostasis depends on the balance between self-renewal of hematopoietic stem cells (HSCs) and their differentiation into blood cell progenitors. A variety of different intrinsic or extrinsic regulators, including multiple microRNA (miRNA) species, have been described to play a role in the regulation of these processes. Disruption of any of these regulators could lead to stem cell exhaustion or increased risk of leukemogenesis. Given recent reports of the role of miR-146a in malignant hematopoiesis, we evaluated its role in hematopoietic stem progenitor cell (HSPC) function. We show that miR-146a is highly expressed in HSCs and its expression decreases in committed progenitors. miR-146a- deficient HSCs had dramatically reduced self-renewal capacity as measured by serial competitive bone marrow transplantation assays. The lower self-renewal capacity was accompanied by decreased quiescence in miR-146a-deficient cells, as revealed by decreased proportion of miR-146a-/- HSPCs ...
To clarify the molecular pathways governing hematopoietic stem cell (HSC) development, we screened a fetal liver (FL) HSC cDNA library and identified a unique gene, hematopoietic expressed mammalian polycomb (hemp), encoding a protein with a zinc-finger domain and four malignant brain tumor (mbt) repeats. To investigate its biological role, we generated mice lacking Hemp (hemp−/−). Hemp−/− mice exhibited a variety of skeletal malformations and died soon after birth. In the FL, hemp was preferentially expressed in the HSC and early progenitor cell fractions, and analyses of fetal hematopoiesis revealed that the number of FL mononuclear cells, including HSCs, was reduced markedly in hemp−/− embryos, especially during early development. In addition, colony-forming and competitive repopulation assays demonstrated that the proliferative and reconstitution abilities of hemp−/− FL HSCs were significantly impaired. Microarray analysis revealed alterations in the expression levels of ...
Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation. Here, we demonstrate that RA decreases gata1 expression and blocks primitive hematopoiesis in zebrafish (Danio rerio) embryos, while increasing expression of the vascular marker, fli1. Treatment with an inhibitor of RA biosynthesis or a retinoic acid receptor antagonist increases \(gata1^+\) erythroid progenitors in the posterior mesoderm of wild-type embryos and anemic \(cdx4^{−/−}\) mutants, indicating a link between the cdx-hox signaling pathway and RA. Overexpression of scl, a DNA binding protein necessary for hematopoietic development, rescues the block of hematopoiesis induced by RA. We show that these effects of RA and RA pathway inhibitors are conserved during ...
TY - JOUR. T1 - Reconstitution of hematopoiesis following transplantation into neonatal mice.. AU - Johnson, Scott A.. AU - Yoder, Mervin C.. PY - 2005. Y1 - 2005. N2 - The primary sites of hematopoiesis change during murine ontogeny. The first blood cells emerge in two waves in the yolk sac; primitive erythroblasts, megakaryocytes, and macrophages emerge on embryonic d (E) 7.0, whereas definitive progenitor cells appear as clusters within the yolk sac vasculature on E8.25. Of interest, yolk sac cells isolated prior to d 10.5 fail to engraft in myeloablated adult recipient mice and do not reconstitute hematopoiesis. We describe a method of sublethally myeloablating newborn mice in which E9.0 yolk sac cells engraft and repopulate all lineages of the hematopoietic system for up to 12 mo in primary recipients and up to 6 mo in secondary recipients. The exact mechanisms that permit yolk sac engraftment in the conditioned newborn mice remain elusive, but this method has been used by a number of ...
Arrayit Hematopoietic Stem Cells and Hematopoiesis Pathways™ Focused Human Genome Microarrays contain 89 genes selected for targeted studies of the human hematopoietic stem cells and hematopoiesis pathway. Arrayit Pathways™ Microarrays gene content is derived from our H25K Whole Human Genome Microarray constructed using highly optimized and unique long-mer oligonucleotides designed to maximize detection of the greatest number of cellular transcripts in the human transcriptome with greater
Granulocytopoiesis definition. granulocytopoiesis gran·u·lo·cy·to·poi·e·sis (grānyə-lō-sītə-poi-ēsĭs) n. See granulopoiesis. granu·lo·cyto·poi·etic (-ětĭk) adj.
Casadevall N. (1995). Cellular mechanism of resistance to erythropoietin. Nephrol Dial Transplant. 10 Suppl 6:27-30.. Erythropoiesis is controlled by different regulators. Interleukin 3, granulocyte-macrophage colony-stimulating factor and stem cell factor play regulatory functions in the early steps of erythropoiesis. Erythropoietin (Epo) is the main factor which acts positively on the last steps of the production of erythrocytes in mammals. Epo is specific for the erythroid progenitor cells and has only little effect on other cells. The target cells for Epo are the erythroid progenitors (BFUe and CFUe). Epo acts on these progenitors through surface receptors specific for Epo. Epo induces the proliferation and differentiation of erythroid progenitors leading finally to reticulocytes. During this process, certain conditions are required to permit this differentiation: progenitors must be present in sufficient numbers, the bone marrow environment must be normal, and nutrients such as folic acid, ...
Two studies by Walkley et al. investigated the role of intrinsic and extrinsic factors in regulating cell cycle and fate of hematopoietic stem cells (HSCs), which reside in specialized niches in the bone marrow and give rise to the cells of the hematopoietic system (see Perry and Li). Although most HSCs maintain a relatively quiescent state, they can be stimulated to enter the cell cycle when hematopoiesis is required. The retinoblastoma (RB) tumor suppressor plays a critical role in cell cycle regulation and, in the first study, Walkley et al. examined the effects of Rb deletion on hematopoiesis. Widespread loss of RB throughout the mouse hematopoietic system led to profound myeloproliferation, characterized by an increase in the numbers of circulating progenitor cells and extramedullary hematopoiesis. There was a loss of trabecular bone (a HSC niche) and HSCs from the bone marrow, and eventual hematopoietic failure. When RB loss was restricted to cells of the myeloid lineage (granulocytes, ...
TY - JOUR. T1 - K-ras/PI3K-Akt signaling is essential for zebrafish hematopoiesis and angiogenesis. AU - Liu, Lihui. AU - Zhu, Shizhen. AU - Gong, Zhiyuan. AU - Low, Boon Chuan. PY - 2008/8/6. Y1 - 2008/8/6. N2 - The RAS small GTPases orchestrate multiple cellular processes. Studies on knock-out mice showed the essential and sufficient role of K-RAS, but not N-RAS and H-RAS in embryonic development. However, many physiological functions of K-RAS in vivo remain unclear. Using wild-type and fli1:GFP transgenic zebrafish, we showed that K-ras-knockdown resulted in specific hematopoietic and angiogenic defects, including the impaired expression of erythroid-specific gene gatal and βe3-hemoglobin, reduced blood circulation and disorganized blood vessels. Expression of either K-rasC40 that links to phosphoinositide 3-kinase (P13K) activation, or Akt2 that acts downstream of P13K, could rescue both hematopoietic and angiogenic defects in the K-ras knockdown. Consistently, the functional rescue by ...
Smurf2 regulates hematopoietic stem cell self-renewal and aging.: The age-dependent decline in the self-renewal capacity of stem cells plays a critical role in
Hematopoiesis is the process of blood cell proliferation and differentiation from multipotent hematopoietic stem cells (HSCs). HSCs are capable of self-renewal as well as differentiation into all mature blood cells. HSCs initially differentiate into lymphoid and myeloid progenitor cells. Lymphoid progenitors differentiate into natural killer cells and lymphocytes (B cells and T cells). Myeloid progenitors differentiate into 4 cell classes: erythrocytes, mast cells, megakaryocytes (which form platelets), and myeloblasts. Myeloblasts differentiate into basophils, neutrophils, eosinophils, and monocytes (which later mature into macrophages). Most blood cells develop and mature in the bone marrow, with the exception of T cells, which develop in the bone marrow and migrate to the thymus for final maturation. Hematopoietic cells play important roles in oxygen dispersal, hemostasis, and immunity. Hematopoietic dysregulation can result in an excess or a lack of certain blood cell types, leading to ...
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TY - JOUR. T1 - A PI3K p110β-Rac signalling loop mediates Pten-loss-induced perturbation of haematopoiesis and leukaemogenesis. AU - Yuzugullu, Haluk. AU - Baitsch, Lukas. AU - Von, Thanh. AU - Steiner, Allison. AU - Tong, Haoxuan. AU - Ni, Jing. AU - Clayton, Linda K.. AU - Bronson, Roderick. AU - Roberts, Thomas M.. AU - Gritsman, Kira. AU - Zhao, Jean J.. PY - 2015/10/7. Y1 - 2015/10/7. N2 - The tumour suppressor PTEN, which antagonizes PI3K signalling, is frequently inactivated in haematologic malignancies. In mice, deletion of PTEN in haematopoietic stem cells (HSCs) causes perturbed haematopoiesis, myeloproliferative neoplasia (MPN) and leukaemia. Although the roles of the PI3K isoforms have been studied in PTEN-deficient tumours, their individual roles in PTEN-deficient HSCs are unknown. Here we show that when we delete PTEN in HSCs using the Mx1-Cre system, p110β ablation prevents MPN, improves HSC function and suppresses leukaemia initiation. Pharmacologic inhibition of p110β in ...
In the same year, this group also clarified that ESAM-deficient mice treated with an anti-tumor drug died before hematopoietic recovery. (Normally, red and white blood cells temporarily decrease after the administration of the anti-tumor drug and recover later.) They were aware that ESAM had an important function, but could not identify the role of ESAM during fetal life.. In this study, the group found that the adult-type hemoglobin synthesis ability of ESAM-null fetal livers was lower than that of wild-type mice and that expression of adult-type hemoglobin-related genes markedly decreased in ESAM-null HSCs. From these findings, they elucidated that ESAM played an important role in the development of definitive hematopoiesis, particularly of adult-type erythropoiesis.. In HSCs co-cultured with a murine stromal cell line, ESAM-null HSCs exhibited functional disruption of differentiation into adult-type blood cells. In fetuses from conditional ESAM-knockout mice, in which ESAM was deficient ...
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TY - JOUR. T1 - Receptor tyrosine kinases and the regulation of hematopoiesis. AU - Paulson, Robert F.. AU - Bernstein, Alan. N1 - Funding Information: We would like to thank members of the Bernstein laboratory for stimulating discussions, and Amy Paulson for excellent editorial help. Work in the Bernstein laboratory is supported by grants from the National Cancer Institute of Canada, the Medical Research Council of Canada, and Bristol-Myers Squibb. A.B. is an International Research Scholar of the Howard Hughes Medical Institute. R.F.P. is a David C. Rae Memorial Fellow of the Leukemia Research Fund of Canada. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1995. Y1 - 1995. N2 - The ongoing production of mature blood cells during the lifetime of an animal is vital for survival. Hematopoesisis the complex process whereby a small population of pluripotential stem cells give rise to mature cell types with specialized functions. The development of mature blood cells proceeds in a ...
Because of artifacts in the preparations, not every cell can be unequivocally classified. You should look for characteristic examples of the various stages of erythrocytic and myeloid development, and know the patterns of blood cell formation. You should also be aware that different texts may use different names for similar stages in blood development. The examples in your own class set will have abnormal cells and many plasma cells since most of these are taken from patients with various types of blood disorders (slide A-4 - Human bone marrow, H&E [2.5x, 10x-labeled, 20x, 40x] [10x, 20x-labeled, 40x] [2.5x, 10x, 20x, 40x]; A-5 - Human bone marrow, Wrights stain with Giemsa [10x, 20x, 40x, 40x, 40x, 40x] [40x, 40x, 40x, 40x, 40x, 40x, 40x]). The red marrow of adult human bones is the major site of formation of erythrocytes, granulocytes, monocytes, and platelets. The most frequent precursor series is the erythroid cell series with the neutrophilic series being second in frequency and ...
Because of artifacts in the preparations, not every cell can be unequivocally classified. You should look for characteristic examples of the various stages of erythrocytic and myeloid development, and know the patterns of blood cell formation. You should also be aware that different texts may use different names for similar stages in blood development. The examples in your own class set will have abnormal cells and many plasma cells since most of these are taken from patients with various types of blood disorders (slide A-4 - Human bone marrow, H&E [2.5x, 10x-labeled, 20x, 40x] [10x, 20x-labeled, 40x] [2.5x, 10x, 20x, 40x]; A-5 - Human bone marrow, Wrights stain with Giemsa [10x, 20x, 40x, 40x, 40x, 40x] [40x, 40x, 40x, 40x, 40x, 40x, 40x]). The red marrow of adult human bones is the major site of formation of erythrocytes, granulocytes, monocytes, and platelets. The most frequent precursor series is the erythroid cell series with the neutrophilic series being second in frequency and ...
The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo. Moreover, we found that hMSC-coated scaffolds can be modulated to form humanized bone tissue, which was also able to support human HSC engraftment. Importantly, hMSC-coated humanized scaffolds were able to support the growth of leukemia patient cells in vivo, including the growth of samples that would not engraft the BM of immunodeficient mice. These results demonstrate that an s.c. implantation ...
2017 begins with a successful PhD defense. Congratulations to Dr. rer. nat. Erik Pittermann, for graduating from the HBRS Regenerative Sciences PhD program within the REBIRTH Cluster of Excellence. He received a magna cum laude grade for his defense of his PhD thesis, titled Modeling Kostmann disease in vitro using iPSC technology.. Kostmann disease (a.k.a. congenital neutropenia) is a rare inherited childhood disorder of white blood cell formation. Eriks PhD work focused on using patient-derived induced pluripotent stem cells (iPSCs) - which have unlimited differentiation potential and can be steered towards any cell type of the human body - to recapitulate and study the Kostmann disease phenotype in vitro. Using CRISPR-Cas9 genome editing, Erik was able to correct the causative genetic mutation, after which proper white blood cell formation and function was restored. He also identified multiple regulatory networks downregulated in Kostmann disease, which were re-expressed upon gene repair ...
Studying embryonic hematopoiesis is complicated by diversity of its locations in the constantly changing anatomy and by the mobility of blood cell precursors. Embryonic hematopoietic progenitors are identified in traditional in vivo and in vitro cell potential assays. Profound epigenetic plasticity of mammalian embryonic cells combined with significant inductive capacity of the potential assays suggest that our understanding of hematopoietic ontogenesis is substantially distorted. Non-invasive in vivo cell tracing methodology offers a better insight into complex processes of blood cell specification. In contrast to the widely accepted view based on the cell potential assays, the genetic tracing approach identified the yolk sac as the source of adult hematopoietic stem cell lineage. Realistic knowledge of the blood origin is critical for safe and efficient recapitulation of hematopoietic development in culture.
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Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, ...
Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, ...
Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, ...
Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, ...
The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA-2 physiological activities necessitate that it be strictly regulated, and cell type-specific enhancers fulfill this role. The +9.5 intronic enhancer harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic in humans. Since mechanisms underlying how GATA2 enhancer disease mutations impact hematopoiesis and pathology are unclear, we generated mouse models of the enhancer mutations. While a multi-motif mutant was embryonically lethal, a single-nucleotide Ets motif mutant was viable, and steady-state hematopoiesis was normal. However, the Ets motif mutation abrogated stem/progenitor cell regeneration following stress. These results reveal a new mechanism in human genetics, in which a disease ...
The development and function of stem and progenitor cells that produce blood cells are vital in physiology. GATA-binding protein 2 (GATA2) mutations cause GATA-2 deficiency syndrome involving immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA-2 physiological activities necessitate that it be strictly regulated, and cell type-specific enhancers fulfill this role. The +9.5 intronic enhancer harbors multiple conserved cis-elements, and germline mutations of these cis-elements are pathogenic in humans. Since mechanisms underlying how GATA2 enhancer disease mutations impact hematopoiesis and pathology are unclear, we generated mouse models of the enhancer mutations. While a multi-motif mutant was embryonically lethal, a single-nucleotide Ets motif mutant was viable, and steady-state hematopoiesis was normal. However, the Ets motif mutation abrogated stem/progenitor cell regeneration following stress. These results reveal a new mechanism in human genetics, in which a disease ...
Insights into the clonal inventory of gene corrected human SCID-X1 hematopoiesis [Elektronische Ressource] / vorgelegt von Jingqiong Hu : Aus dem Institut für Molekulare Medizin und Zellforschung der Albert-Ludwigs-Universität Freiburg i. Br. INSIGHTS INTO THE CLONAL INVENTORY OF GENE CORRECTED HUMAN SCID-X1 HEMATOPOIESIS INAUGURAL-DISSERTATION zur Erlangung des Medizinischen Doktorgrades der Medizinischen Fakultät der Albert-Ludwigs-Universität Freiburg i. Br. vorgelegt
The crucial checkpoints that determine T-cell fate along with various differentiation pathways have been genetically defined. Still there are many uncharacterized genes whose roles in thymus and T cell development have yet to be established. One such example is Thymocyte specific cAMP-regulated phosphoprotein (thymocyte Arpp21 or Tarpp). Although TARPP protein is highly expressed in immature T cells and is down-regulated immediately after T-cell receptor (TCR) gene rearrangements, Tarpp KO mice did not have any apparent immunological phenotype. We hypothesized that two other proteins sharing high homology and RNA-binding domains with TARPP, R3h-domain containing protein 1 and 2 (R3HDM1 and R3HDM2) are able to compensate its function in vivo. Through generation of R3hdm1 and R3hdm2 KO mice, we intended to characterize role of these two RNA-binding proteins in murine hematopoiesis. R3hdm1, R3hdm2 and newly derived Tarpp KO (-/-) mice were viable but surprisingly did not have any immunological ...
The immunosuppressive tumor microenvironment represents a major hurdle to cancer therapy. We developed a gene transfer strategy into hematopoietic stem cells (HSCs) to target transgene expression to tumor-infiltrating monocytes/macrophages. Using a combination of transcriptional and microRNA-mediated control, we achieved selective expression of an interferon-α (IFN-α) transgene in differentiated monocytes of human hematochimeric mice. We show that IFN-α transgene expression does not impair engraftment and long-term multilineage repopulation of NSG (NOD/LtSz-scidIL2Rγ(null)) mice by transplanted human HSCs. By providing a source of human cytokines in the mice, we improved the functional reconstitution of human myeloid, natural killer, and T cell lineages, and achieved enhanced immune-mediated clearance of transplanted human breast tumors when hematopoiesis was engineered for tumor-targeted IFN-α expression. By applying our strategy to mouse breast cancer models, we achieved inhibition of ...
Controlled self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs) are critical for vertebrate development and survival. These processes are tightly regulated by the transcription factors, signaling molecules, and epigenetic factors. Impaired regulations of their function could result in hematological malignancies. Using a large-scale zebrafish N-ethyl-N-nitrosourea (ENU) mutagenesis screening, we identified a line named LDD731, which presented significantly increased HSPCs in hematopoietic organs. Further analysis revealed that the erythoid/myeloid lineages in definitive hematopoiesis were increased while the primitive hematopoiesis was not affected. The homozygous mutation was lethal with a median survival time around 14-15 days post-fertilization. The causal mutation was located by positional cloning in the c-cbl gene, of which the human ortholog, c-CBL, is found frequently mutated in myeloproliferative neoplasms (MPN) or acute leukemia. Sequence analysis showed the ...
CDK4/6 inhibitors are considered a breakthrough in cancer therapy. Currently approved for breast cancer treatment, CDK4/6 inhibitors are extensively tested in other cancer subtypes. Frequently observed side effects include hematological abnormalities such as reduced numbers of neutrophils, erythroid cells and platelets that are associated with anemia, bleedings and a higher risk of infections. To understand whether the adverse effects within the hematopoietic system are related to CDK4 or CDK6 we generated transgenic mice that lack either CDK4 or CDK6 in adult hematopoiesis. Anemia and perturbed erythroid differentiation are associated with the absence of CDK6 but did not manifest in CDK4-deficient mice. Total CDK6 knockout mice accumulate the most dormant fraction of hematopoietic stem cells due to an impaired exit of the quiescent state. We recapitulated this finding by deleting CDK6 in adult hematopoiesis. In addition, unlike total CDK6 knockout, all stem cell fractions were affected and ...
Zon adopted the zebrafish as a model organism largely because fertilization occurs exogenously, which makes it much easier to study blood development during early growth in the external embryo. I wanted a period of time when there werent blood cells and a period of time when these arose, so that I could study that process, Zon commented. He argued that the zebrafish is as good as any other vertebrate model, including humans, for studying the fundamental mechanisms of blood development: I now think all vertebrates are equally complex as far as the blood system is concerned.. Zon conceded that this observation does not apply to complex neuronal function; but that even here, animal models have helped to elucidate many of the pathways underpinning the more complex behavioural functions of higher mammals. Jerry Yin, Professor of Genetics and Psychiatry at the University of Wisconsin‐Madison (Madison, WI, USA), chose to use Drosophila to study the molecular mechanisms of learning and memory ...
HIV infection has been associated with defective hematopoiesis since the earliest days of the HIV/AIDS epidemic. Generation of all hematopoietic lineages suffers in the face of infection. The mechanisms by which HIV impairs normal blood cell development remain unclear, and direct infection of intermediate hematopoietic progenitors has not been established as a source of HIV-associated hematopoietic pathology. Here, we demonstrate infection of multiple subsets of highly purified intermediate hematopoietic progenitors by wild-type HIV both in vitro and in vivo. Although direct infection is clearly cytotoxic, we find that some infected progenitors can survive and harbor proviral DNA. We report intermediate hematopoietic progenitors to be a novel target of infection and their permissivity to infection increases with development. Further, the nonobese diabetic severe combined immunodeficiency common γ chain knockout-bone marrow-liver-thymus humanized mouse provides a unique model for studying the ...
Chronic oral toxicity studies were conducted in rats (2 years), dogs (47 weeks; 1 year), mice (2 years), and monkeys (1 year). Significant drug-related toxicity included effects on hematopoiesis, renal toxicity, erosion/ulceration of the stomach, and variation of retinal blood vessels. Reductions in hemoglobin and/or hematocrit values were seen in mice, rats, and monkeys at doses 50 to 150 times the maximum recommended human dose (MRHD) of 450 mg, assuming a 50-kg subject. On a body-surface-area basis, these doses are 5 to 25 times maximum recommended dose (MRHD). Anemia, leukopenia, thrombocytopenia, and bone marrow suppression occurred in dogs at doses 8 to 30 times MRHD on a body-weight basis (4 to 15 times MRHD on a surface-area basis). The reductions in hemoglobin and hematocrit values in rats and mice were only significant at 1 year and returned to normal with continued dosing by the end of the study. Marked anemia was seen at all dose levels (8 to 30 times MRHD) in dogs, whereas moderate ...
Fer kinase, a protein involved in the regulation of cell-cell adhesion and proliferation, has been shown to be required during invertebrate development and has been implicated in leukemia, gastric cancer, and liver cancer. However, in vivo roles for Fer during vertebrate development have remained elusive. In this study, we bridge the gap between the invertebrate and vertebrate realms by showing that Fer kinase is required during zebrafish embryogenesis for normal hematopoiesis and vascular organization with distinct kinase dependent and independent functions. In situ hybridization, quantitative PCR and fluorescence activated cell sorting (FACS) analyses revealed an increase in both erythrocyte numbers and gene expression patterns as well as a decrease in the organization of vasculature endothelial cells. Furthermore, rescue experiments have shown that the regulation of hematopoietic proliferation is dependent on Fer kinase activity, while vascular organizing events only require Fer in a kinase
Hematopoiesis[edit]. Duffy antigen plays a fundamental role on hematopoiesis.[80] Indeed, nucleated red blood cells present in ... The absence of erythroid DARC alters hematopoiesis including stem and progenitor cells, which ultimately gives rise to ... alternative physiological patterns of hematopoiesis and bone marrow cell outputs depend on the expression of DARC in the ... "Atypical chemokine receptor 1 on nucleated erythroid cells regulates hematopoiesis". Nature Immunology. 18 (7): 753-761. doi ...
Jagannathan-Bogdan, Madhumita; Zon, Leonard I. (2013-06-15). "Hematopoiesis". Development. 140 (12): 2463-2467. doi:10.1242/dev ... causes extramedullary hematopoiesis in the fetal liver and bone marrow. The push to make more erythroblasts to help compensate ...
When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and thus slow down clot formation by preventing the conversion of fibrinogen to fibrin. This effect can be seen in the thrombin clotting time (TCT) test, which is prolonged in a person that has active fibrinolysis.. FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and confirms that fibrinolysis has occurred. It is therefore used to indicate deep-vein thrombosis, pulmonary embolism, DIC and efficacy of treatment in acute myocardial infarction. Alternatively, a more rapid detection of fibrinolytic activity, especially hyperfibrinolysis, is possible with thromboelastometry (TEM) in whole blood, even in patients on heparin. In this assay, increased fibrinolysis is assessed by comparing the TEM profile in the absence or presence of the fibrinolysis inhibitor aprotinin. ...
Members of every class of pathogen that infect humans also infect plants. Although the exact pathogenic species vary with the infected species, bacteria, fungi, viruses, nematodes, and insects can all cause plant disease. As with animals, plants attacked by insects or other pathogens use a set of complex metabolic responses which lead to the formation of defensive chemical compounds that fight infection or make the plant less attractive to insects and other herbivores.[33] (see: plant defense against herbivory). Like invertebrates, plants neither generate antibody or T-cell responses nor possess mobile cells that detect and attack pathogens. In addition, in case of infection, parts of some plants are treated as disposable and replaceable, in ways that very few animals are able to do. Walling off or discarding a part of a plant helps stop spread of an infection.[33] Most plant immune responses involve systemic chemical signals sent throughout a plant. Plants use pattern-recognition receptors to ...
Haematopoiesis. *Immune system. *Innate immune system. *Trogocytosis. *White blood cell. References[edit]. *^ WebMD (2009). " ...
Mikael Häggström is a Doctor of Medicine, and the creator of WikiJournal of Medicine, as well as Radlines. He was born in Gothenburg, Sweden, and is a grandchild of Estonian historian Karin Aasma. He grew up in Uddevalla on the Swedish west coast. He decided to become a doctor while backpacking for half a year in 2005, taking the Trans-Siberian train to China and crossing the Himalayas from Tibet to Nepal. He graduated from Uppsala University, Faculty of Medicine in 2013. He did his internship in Sundsvall, and has worked 1.5 years as a physician in obstetrics and gynecology and 3 years in radiology. He is currently doing specialist training in pathology at the NU Hospital Group, Sweden. He has contributed to Wikipedia since 2006, including a multitude of medical images. He is the creator and current editor-in-chief of WikiJournal of Medicine, a new Wikipedia-integrated, peer-reviewed, open-access academic journal.[1] He is also the creator of Radlines and Patholines, containing open access ...
Orkin SH, Zon LI (February 2008). "SnapShot: hematopoiesis". Cell. 132 (4): 712.e1-712.e2. doi:10.1016/j.cell.2008.02.013. PMID ...
Jan M, Ebert BL, Jaiswal S (January 2017). "Clonal hematopoiesis". Seminars in Hematology. 54 (1): 43-50. doi:10.1053/j. ... a condition known as clonal hematopoiesis, and cardiovascular disease-related incidents and mortality. Radiation treatments for ...
Sites of hematopoiesisEdit. The principal site of extramedullary hematopoiesis in myelofibrosis is the spleen, which is usually ... with foci of extramedullary hematopoiesis. Microscopically, lymph nodes also contain foci of hematopoiesis, but these are ... Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components. It is one of the ... Another complication of extramedullary hematopoiesis is poikilocytosis, or the presence of abnormally shaped red blood cells.[ ...
KDR Hematopoiesis, cyclic; 162800; ELANE Hematuria, benign familial; 141200; COL4A3 Hemiplegic migraine, familial; 141500; ...
... primitive hematopoiesis), islet resident progenitors come from hematopoietic stem cells (HSCs) of the definitive hematopoiesis ... Dzierzak, E (1995). "Mouse embryonic hematopoiesis". Trends Genet. 11 (9): 359-66. doi:10.1016/S0168-9525(00)89107-6. PMID ...
Civin CI, Strauss LC, Brovall C, Fackler MJ, Schwartz JF, Shaper JH (1984). "Antigenic analysis of hematopoiesis. III. A ... Furness SG, McNagny K (2006). "Beyond mere markers: functions for CD34 family of sialomucins in haematopoiesis". Immunologic ...
Kojika S, Griffin JD (2001). "Notch receptors and hematopoiesis". Exp. Hematol. 29 (9): 1041-52. doi:10.1016/S0301-472X(01) ...
... , as well as the rest of haematopoiesis, begins from a haematopoietic stem cells. These are multipotent cells ... Doulatov S, Notta F, Laurenti E, Dick JE (February 2012). "Hematopoiesis: a human perspective". Cell Stem Cell. 10 (2): 120-36 ... Granulopoiesis (or granulocytopoiesis) is a part of haematopoiesis, that leads to the production of granulocytes. A granulocyte ...
"Epigenetic regulation of hematopoiesis". International Journal of Hematology. 96 (4): 405-412. doi:10.1007/s12185-012-1183-x. ... Hence, Polycomb-group genes and proteins are involved in the proper maintenance of hematopoiesis in the body. Jayavelu ND, ... The Polycomb Repressive Complex 1 (PRC 1) is directly involved in the process of hematopoiesis, and functions together with, ...
"Medical Definition of Hematopoiesis". MedicineNet. Archived from the original on 14 March 2017. Retrieved 21 February 2020. "5 ... This process is called haematopoiesis. Hematopoietic stem cells are found in the bone marrow and umbilical cord blood. Mammary ...
1983). Beardsley, Terry R. Patent # 7,196,060; Method to enhance hematopoiesis. Method to enhance hematopoiesis - Google ...
"Entrez Gene: Musashi RNA binding protein 2". de Andrés-Aguayo L, Varas F, Graf T (July 2012). "Musashi 2 in hematopoiesis". ... "Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia" (PDF). Nature Medicine. 16 (8): 903-8. doi: ...
Baron, Margaret H. (2001). "Embryonic Induction of Mammalian Hematopoiesis and Vasculogenesis". In Zon, Leonard I. (ed.). ... Hematopoiesis: a developmental approach. Oxford University Press. ISBN 978-0-19-512450-7. Cullen, K.E. (2009). "embryology and ...
"Volume 9.20 , May 22 - Hematopoiesis News". www.hematopoiesisnews.com. Retrieved 2018-10-11. "Seattle Cancer Care Alliance ...
Beardsley, Terry R. Patent # 7,196,060; Method to enhance hematopoiesis. http://www.google.com/patents?id=wE1_AAAAEBAJ&dq= ...
It is important normal hematopoiesis. GFI1 has been shown to interact with PIAS3 and RUNX1T1. GRCh38: Ensembl release 89: ... role in normal hematopoiesis". Blood. 100 (8): 2769-77. doi:10.1182/blood-2002-01-0182. PMID 12351384. Strausberg RL, Feingold ...
Langemeijer SM, Aslanyan MG, Jansen JH (December 2009). "TET proteins in malignant hematopoiesis". Cell Cycle. 8 (24): 4044-8. ...
Haematopoiesis (from Greek αἷμα, "blood" and ποιεῖν "to make"; also hematopoiesis in American English; sometimes also ... In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it occurs mainly in ... Fernández, KS; de Alarcón, PA (Dec 2013). "Development of the hematopoietic system and disorders of hematopoiesis that present ... Medical Immunology (1 ed.). ISBN 978-0-8385-6278-9. "Hematopoiesis from Pluripotent Stem Cells". ThermoFisher Scientific. ...
There are 2 types of hematopoiesis that occur in humans: Primitive hematopoiesis - blood stem cells differentiate into only a ... highlighting its importance in maintaining hematopoiesis. Hematopoiesis involves a series of differentiation steps from one ... Hematopoiesis then moves from the AGM to the placenta and fetal liver at E11.5 in mice and 5wpc in humans. While the ... Hematopoiesis then moves to the bone marrow at E18 in mice and 12wpc in humans, where it will reside permanently for the ...
SCF plays an important role in the hematopoiesis during embryonic development. Sites where hematopoiesis takes place, such as ... Andrews RG, Briddell RA, Appelbaum FR, McNiece IK (1994). "Stimulation of hematopoiesis in vivo by stem cell factor". Curr. ... Broudy VC (August 1997). "Stem cell factor and hematopoiesis". Blood. 90 (4): 1345-64. doi:10.1182/blood.V90.4.1345. PMID ... This cytokine plays an important role in hematopoiesis (formation of blood cells), spermatogenesis, and melanogenesis. The gene ...
Garzon R, Croce CM (Jul 2008). "MicroRNAs in normal and malignant hematopoiesis". Current Opinion in Hematology. 15 (4): 352-8 ... miR-150 functions in hematopoiesis; it regulates genes whose downstream products encourage differentiating stem cells towards ... "The role of microRNAs in normal and malignant hematopoiesis". European Journal of Haematology. 84 (1): 1-16. doi:10.1111/j.1600 ...
Jones M, Bisht K, Savage SA, Nandakumar J, Keegan CE, Maillard I (2016). "The shelterin complex and hematopoiesis". Journal of ...
2. Hematopoiesis and Resistance to Physical Stress. Boca Raton, Florida: CRC Press, 1981. 594 pp. CRC Handbook of Nutritive ...
Fisher, Robert C.; Scott, Edward W. (1998-01-01). "Role of PU.1 in Hematopoiesis". Stem Cells. 16 (1): 25-37. doi:10.1002/stem. ...
The monophyletic theory on hematopoiesis, which is widely accepted, suggests that all of the hematopoietic cells are generated ... Hematopoiesis is the process by which blood cells are created. ... Hematopoiesis is the process by which blood cells are created. ... Hematopoiesis during the early stages of embryogenesis occurs in the yolk sac and subsequently in the liver. During the 3rd to ... The monophyletic theory on hematopoiesis, which is widely accepted, suggests that all of the hematopoietic cells are generated ...
This volume of Molecular Biology of Hematopoiesis is dedicated to many inter- national scientists and clinicians for their ... This volume of Molecular Biology of Hematopoiesis is dedicated to many inter- national scientists and clinicians for their ... Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, ...
This study explores the prevalence of clonal hematopoiesis related to radioactive iodine exposure and how it impacts overall ... Clonal hematopoiesis (CH) is a precursor clonal state that confers increased risk of leukemia and occurs at an elevated rate in ... Clonal hematopoiesis (CH) refers to recurrent somatic mutations in leukemia-associated genes that are commonly acquired in ... Radioactive Iodine-Related Clonal Hematopoiesis in Thyroid Cancer Is Common and Associated With Decreased Survival. ...
Please Note: All session times for the AACR Virtual Meeting: Clonal Hematopoiesis are U.S. Eastern Daylight Time (EDT). ...
Resolving variant-to-function relationships in hematopoiesis. *Manuel Tardaguila1. & *Nicole Soranzo. ORCID: orcid.org/0000- ... Interrogation of human hematopoiesis at single-cell and single-variant resolution *Jacob C. Ulirsch ... Tardaguila, M., Soranzo, N. Resolving variant-to-function relationships in hematopoiesis. Nat Genet 51, 581-583 (2019). https ...
Hematopoiesis is the process of creating new blood cells in the body. All blood cells start off as hematopoietic stem cells, ... Hematopoiesis is the process of creating new blood cells in the body. All blood cells start off as hematopoietic stem cells, ...
Hox genes in hematopoiesis and leukemogenesis.. Argiropoulos B1, Humphries RK.. Author information. 1. Terry Fox Laboratory, ... The data strongly support the hypothesis that the role of Hox genes in normal hematopoiesis is primarily at the level of ... Given the documented role of Hox genes in hematopoiesis and leukemogenesis, we propose that Hox-dependent pathways are closely ... model have provided strong correlative evidence for the involvement of clustered Hox genes in normal hematopoiesis. ...
hematopoiesis (thing). See all of hematopoiesis, no other writeups in this node. ...
The NIDDK Hematopoiesis and Hematopoietic Stem Cell Biology program focuses on understanding the basic cellular and molecular ... Hematopoiesis & Hematopoietic Stem Cell Biology. The basic cellular and molecular mechanisms underlying the production and ... The Hematopoiesis and Hematopoietic Stem Cell Biology program focuses on understanding the basic cellular and molecular ... Terry Rogers Bishop, Ph.D. Hematology; Stem Cells; Hematopoiesis; Globin; Hematology Centers and Training ...
Hematopoiesis RT2 Profiler PCR Array The Rat Hematopoiesis RT² Profiler PCR Array profiles the expression of 84 genes related ... Hematopoiesis RT2 Profiler PCR Array The Human Hematopoiesis RT² Profiler PCR Array profiles the expression of 84 genes related ... Hematopoiesis RT2 Profiler PCR Array The Mouse Hematopoiesis RT² Profiler PCR Array profiles the expression of 84 genes related ... Hematopoiesis is the process of blood cell proliferation and differentiation from multipotent hematopoietic stem cells (HSCs). ...
... of the population over age 70 has observable clonal hematopoiesis. Having clonal hematopoiesis has been linked to a more than ... Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases ... Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as neutral drift in the stem ... Clonal hematopoiesis does not typically give rise to noticeable symptoms, but does lead to increased risk of cardiovascular ...
Extramedullary hematopoiesis (EMH or sometimes EH) refers to hematopoiesis occurring outside of the medulla of the bone (bone ... Hematopoiesis also takes place in many other tissues or organs such as the yolk sac, the aorta-gonad mesonephros (AGM) region, ... During fetal development, hematopoiesis occurs mainly in the fetal liver and in the spleen followed by localization to the bone ... Pulmonary hematopoiesis also appears to play an important role in adults. In comparison to the bone marrow, where trilineage ...
... is a normal response to failure of hematopoiesis at its normal site i.e., bone marrow. It is a manifestation of many congenital ... Extramedullary hematopoiesis (EMH) is a normal response to failure of hematopoiesis at its normal site i.e., bone marrow. It is ... Intracranial extramedullary hematopoiesis in beta-thalassemia. Korean J Radiol. 2012;13:240.CrossRefPubMedPubMedCentralGoogle ... Kim C. Homeostatic and pathogenic extramedullary hematopoiesis. J Blood Med. 2010;1:13-9.CrossRefPubMedPubMedCentralGoogle ...
Haematopoiesis definition at Dictionary.com, a free online dictionary with pronunciation, synonyms and translation. Look it up ...
hematopoiesis definition: the production of blood cells by the blood-forming organsOrigin of hematopoiesisfrom hemato- + ... hematopoiesis. he·ma·to·poi·e·sis. the production of blood cells by the blood-forming organs ... Hematopoiesis. (n.d.). In YourDictionary. Retrieved from https://www.yourdictionary.com/Hematopoiesis ... Hematopoiesis. (n.d.). In YourDictionary. Retrieved from https://www.yourdictionary.com/Hematopoiesis ...
A) Hematopoiesis occurs first in the yolk sac (YS) blood islands and later at the aorta-gonad mesonephros (AGM) region, ... A) Hematopoiesis occurs first in the intermediate cell mass (ICM) and subsequently in the aorta-go-nad mesonephros (AGM) region ... Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role ... B) Hematopoiesis in each location favors the production of specific blood lineages. Abbreviations: ECs, endothelial cells; RBCs ...
Analysis of the early YS hematopoiesis at 7.5-9.5 dpc or adult hematopoiesis from Cdx1−/− mice did not reveal any obvious blood ... a Hox regulator involved in definitive hematopoiesis (9). During adult hematopoiesis, overexpression of human CDX2 or murine ... Cdx gene deficiency compromises embryonic hematopoiesis in the mouse. Yuan Wang, Akiko Yabuuchi, Shannon McKinney-Freeman, ... Cdx gene deficiency compromises embryonic hematopoiesis in the mouse. Yuan Wang, Akiko Yabuuchi, Shannon McKinney-Freeman, ...
What is clonal hematopoiesis? How does this process affect the development of certain kinds of cancers? Cancer Today explains ... Clonal Hematopoiesis: You Are Not the Same Person You Used to Be. August 29, 2019 by Cancer Today Staff ... Clonal hematopoiesis is rare before age 50 (1 percent of individuals), but it can appear in 10 percent to 20 percent of those ... Of note, clonal hematopoiesis would have been a silent condition were it not recognized via DNA sequencing of blood cells, ...
Normal hematopoiesis. Dynamic clonal hematopoiesis and functional T-cell immunity in a supercentenarian. *Erik B. van den Akker ... van den Akker, E.B., Makrodimitris, S., Hulsman, M. et al. Dynamic clonal hematopoiesis and functional T-cell immunity in a ... Age-related Clonal hematopoiesis (ARCH) is an inevitable consequence of ageing, which arises when an ageing hematopoietic stem ... Clonal hematopoiesis, with and without candidate driver mutations, is common in the elderly. Blood. 2017; blood-2017-02-769869 ...
... which was termed in the past age-related clonal hematopoiesis (ARCH). ARCH is defined as the gradual, clonal expansion of HSPCs ... Age-related clonal hematopoiesis. Blood, 131(5), 496-504. Accessed February 23, 2018. https://doi.org/10.1182/blood-2017-07- ...
Hematopoiesis Is the Subject Area "Hematopoiesis" applicable to this article? Yes. No. ...
Buy the Hardcover Book Hematopoiesis by Emery Bresnick at Indigo.ca, Canadas largest bookstore. + Get Free Shipping on Science ... Hematopoiesis, the latest volume in theCurrent Topics in Developmental Biology,covers hematopoiesis, with contributions from an ... Title:HematopoiesisFormat:HardcoverDimensions:292 pages, 9.41 × 7.24 × 0.98 inPublished:April 27, 2016Publisher:Academic Press ... 6. SCL/TAL1 in Hematopoiesis and Cellular Reprogramming. Trang Hoang, Julie A Lambert and Richard Martin. 7. Navigating ...
The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis T. Michael Creed, ... The role of variant histone H2AV in Drosophila melanogaster larval hematopoiesis Melina Grigorian, Heather DeBruhl, Joseph S. ... Summary: A new model for understanding the earliest steps of hematopoiesis is based on the in vitro recapitulation of hemogenic ... Summary: Discovery of novel PAX-SIX-EYA-DACH and GATA network interactions in Drosophila hematopoiesis reveal that human SIX ...
Primary myelofibrosis (PMF) is a clonal hematologic malignancy characterized by BM fibrosis, extramedullary hematopoiesis, ...
The nuclear protein DEK is an endogenous DNA-binding chromatin factor regulating hematopoiesis. DEK is one of only 2 known ... To determine whether extracellular DEK required nuclear function to regulate hematopoiesis, we utilized 2 mutant forms of DEK: ... secreted nuclear chromatin factors, but whether and how extracellular DEK regulates hematopoiesis is not known. We demonstrated ...
... The CT scan of the chest revealed well-defined bilateral paraspinal masses in the lower ... Extramedullary hematopoiesis occurs as a compensatory mechanism for abnormal hematopoiesis when normal red marrow is unable to ... Extramedullary hematopoiesis should be considered in the differential diagnosis in a patient with chronic severe anemia and a ... Extramedullary hematopoiesis is the production of blood elements outside the bone marrow cavity. Until 20 weeks of prenatal ...
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Erythropoietin couples hematopoiesis with bone formation.. [Yusuke Shiozawa, Younghun Jung, Anne M Ziegler, Elisabeth A ... and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow. ...
Hematopoiesis and immune cell cancer. Research into the signalling mechanisms involved in hematopoiesis and the pathogenesis of ... Hematopoiesis and immune cell cancer. Research into the signalling mechanisms involved in hematopoiesis and the pathogenesis of ... Hematopoiesis is a complex but precisely regulated process that gives rise to blood cells of all lineages. Hematopoietic stem ... Home / Research and expertise / Biomedical Research Group / Hematopoiesis and immune cell cancer. ...
  • Advances in model systems, genome-editing tools, single-cell analyses, and imaging technologies have provided insight into the molecular, cellular, and developmental basis of normal and malignant hematopoiesis. (keystonesymposia.org)
  • Taken together, participants at this conference will gain new insight into the biology of normal and malignant hematopoiesis and cutting-edge technologies, as well as have opportunities to cultivate new ideas and establish collaborations with researchers from disparate disciplines. (keystonesymposia.org)
  • This article discusses the recent advances in our knowledge of the microenvironment supporting malignant hematopoiesis, including LSC niche. (frontiersin.org)
  • The importance of mouse models in elucidating the role of Flt3-ligand in normal and malignant hematopoiesis is discussed. (mdpi.com)
  • This review summarizes current knowledge regarding the function of TGF-beta in normal and malignant hematopoiesis. (nih.gov)
  • Therefore c-abl may be important in normal as well as malignant hematopoiesis. (sciencemag.org)
  • This is called extramedullary haematopoiesis . (thefullwiki.org)
  • Extramedullary haematopoiesis: an uncommon posterior mediastinal mass. (thefreelibrary.com)
  • The CT features were typical of extramedullary haematopoiesis (EMH). (thefreelibrary.com)
  • The CT features were typical of extramedullary haematopoiesis (EMH), defined as the development and growth of haematopoietic tissue outside the bone marrow. (thefreelibrary.com)
  • Extramedullary haematopoiesis (EMH) is the formation of cellular components of blood, occurring outside of the bone marrow. (bmj.com)
  • It is imperative to consider extramedullary haematopoiesis when adrenal enlargement is seen in patients with haematological disorders, such as thalassemia. (bmj.com)
  • MEETING CHANGE TO VIRTUAL eSymposia: https://virtual.keystonesymposia.org/ks/live/726/page/6781 Hematopoiesis is a highly regulated and dynamic developmental process by which hematopoietic stem cells self-renew and differentiate to form all blood lineages. (keystonesymposia.org)
  • This Keystone Symposia conference brings together basic and translational researchers to discuss and debate emerging topics and recent advances on developmental hematopoiesis, adult stem cell self-renewal and stem cell niches, novel hematopoietic regulators, and the pathogenesis of bone marrow failure syndromes and leukemia. (keystonesymposia.org)
  • C) Developmental timewindows for shifting sites of hematopoiesis. (nih.gov)
  • Hematopoiesis , the latest volume in the Current Topics in Developmental Biology, covers hematopoiesis, with contributions from an international board of authors. (indigo.ca)
  • After presenting the principles of developmental hematopoiesis, the atlas focuses on lineage-specific processes. (springer.com)
  • Using an in vitro system of mouse ES cell differentiation into cardiomyocytes, we show here that Wnt/β-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiomyogenesis and hematopoiesis/vasculogenesis. (pnas.org)
  • Thus, Wnt/β-catenin signaling exhibits developmental stage-specific, biphasic, and antagonistic effects on cardiogenesis and hematopoiesis/vasculogenesis, and appropriate modulation of Wnt signaling enables highly efficient cardiomyocyte differentiation of ES cells. (pnas.org)
  • If we can further our understanding of developmental hematopoiesis and identify key regulators of these processes in vivo, it may be possible to apply this knowledge to in vitro efforts to derive patient-specific HSCs from induced pluripotent stem cells (iPSCs). (rupress.org)
  • Developmental hematopoiesis: ontogeny, genetic programming and conservation. (xenbase.org)
  • Here, we discuss the key contributions of these model organisms to our understanding of developmental hematopoiesis. (xenbase.org)
  • Given that many of the regulatory genes that control embryonic hematopoiesis have been implicated in oncogenic pathways in adults, an understanding of blood cell ontogeny is likely to provide insights into the pathophysiology of human leukemias. (nih.gov)
  • A group of researchers at Osaka University revealed that ESAM (Endothelial cell-selective adhesion molecule), a surface marker for hematopoietic stem cells (HSCs) and vascular endothelial cells (ECs), played an important role in the ontogeny of hematopoiesis in mice, particularly in the development of adult-type erythropoiesis. (innovations-report.com)
  • This shows the contribution of ESAM to the ontogeny of definitive hematopoiesis and the functional involvement of ESAM-expressing endothelial cells. (innovations-report.com)
  • The ontogeny of hematopoiesis in zebrafish. (biologists.org)
  • Clonal hematopoiesis of indeterminate potential, or CHIP, is a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells. (wikipedia.org)
  • This has prompted some to name the condition clonal hematopoiesis of indeterminate potential (CHIP). (aacr.org)
  • When a substantial proportion of the blood cells carries such a pre-leukemic mutation in an otherwise normal immuno-hematopoietic system, this state is also referred to as Clonal Hematopoiesis of Indeterminate Potential [ 3 ]. (nature.com)
  • The Human Hematopoiesis RT² Profiler PCR Array profiles the expression of 84 genes related to the development of blood-cell lineages from HSCs through progenitor stem cells. (qiagen.com)
  • This is the first atlas dedicated to illustrating the cellular and molecular mechanisms that underlie the unique features of human hematopoiesis during embryonic, fetal, and neonatal developments. (springer.com)
  • p120 GAP requirement in normal and malignant human hematopoiesis. (rupress.org)
  • Here, we show that the Integrator complex, an evolutionarily conserved group of proteins, functions in zebrafish hematopoiesis by modulating Smad/BMP signaling. (biologists.org)
  • During development, vertebrates go through a primitive and a definitive phase of hematopoiesis. (wikipedia.org)
  • Definitive hematopoiesis differs from the primitive phase through the production of hematopoietic stem cells. (wikipedia.org)
  • In mice, the first wave of primitive yolk sac (YS) hematopoiesis occurs before 7.5 days postcoitum (dpc), followed by a second wave of definitive hematopoiesis in the aorta-gonad-mesonephros (AGM) region, which then relocates to fetal liver before birth ( 1 ). (pnas.org)
  • In addition, Cdx4 overexpression rescues defective blood progenitor formation in mouse ESCs deficient in the Mll , a Hox regulator involved in definitive hematopoiesis ( 9 ). (pnas.org)
  • Here, we provide a detailed review of the timing, anatomical location, and transcriptional regulation of zebrafish 'primitive' and 'definitive' hematopoiesis as well as discuss a model of T-cell leukemia and recent advances in blood cell transplantation. (nih.gov)
  • From these findings, they elucidated that ESAM played an important role in the development of definitive hematopoiesis, particularly of adult-type erythropoiesis. (innovations-report.com)
  • That is, both ESAM expressed on HSCs and ESAM expressed on ECs play an important role in developing definitive hematopoiesis. (innovations-report.com)
  • Both the Cbfa2 and Cbfb genes are essential for normal hematopoiesis in mice, because homozygous disruption of either gene blocks definitive hematopoiesis. (aacrjournals.org)
  • We show that LRP2 is indeed involved in definitive hematopoiesis and by doing so validate the use of reporter gene coupled enhancers as probes to gain insights into transcriptional changes that facilitate cell fate transitions. (mdc-berlin.de)
  • During adult hematopoiesis, overexpression of human CDX2 or murine Cdx4 alone results in acute myeloid leukemia in mice ( 10 , 11 ). (pnas.org)
  • Primary myelofibrosis (PMF) is a clonal hematologic malignancy characterized by BM fibrosis, extramedullary hematopoiesis, circulating CD34 + cells, splenomegaly, and a propensity to evolve to acute myeloid leukemia. (jci.org)
  • NEW YORK - A team led by researchers at Memorial Sloan Kettering Cancer Center has uncovered clonal hematopoiesis patterns and genetic mutations that may contribute to the development of new tumors after cancer treatment, known as therapy-related myeloid neoplasms (tMNs). (genomeweb.com)
  • In patients with acute myeloid leukemia (AML), the production of healthy blood cells from hematopoietic stem cells in the bone marrow (a process called hematopoiesis) is suppressed, prompting the need for bone marrow transplants. (sciencemag.org)
  • Extramedullary hematopoiesis, or myeloid metaplasia, is a frequently encountered condition, occurring usually in association with certain types of anemia. (annals.org)
  • Receptorn har dock visat sig vara muterad i akut myeloid leukemi (AML), och associerad med en sämre prognos. (lu.se)
  • Interestingly, CoCl2 also decreased CFU-G together with CFU-GM but increased CFU-M number in fetal haematopoiesis in the same manner as DFO in acute myeloid leukaemia study (Callens et al. (muni.cz)
  • 2010). In contrast, in adult hematopoietic progenitors CoCl2 increased number of CFU-G and CFU-GM but decreased CFU-M. In summary, our results show HIF-1alpha dependent regulation of both overall haematopoiesis and myeloid lineage directed differentiation. (muni.cz)
  • Moreover, the results of myeloid differentiation in response to CoCl2 in adult and fetal haematopoiesis may indirectly support recent hypothesis, that tumor cells may have the phenotype of fetal progenitors rather than the phenotype of adult lineage progenitors. (muni.cz)
  • Hematopoiesis is the process of blood cell proliferation and differentiation from multipotent hematopoietic stem cells (HSCs). (qiagen.com)
  • Hematopoiesis is a process that includes the formation, maturation, and differentiation of blood cells. (intechopen.com)
  • For the stem cells and other undifferentiated blood cells in the bone marrow, the determination is generally explained by the determinism theory of haematopoiesis, saying that colony stimulating factors and other factors of the haematopoietic microenvironment determine the cells to follow a certain path of cell differentiation. (thefullwiki.org)
  • Like IL-1, IL-6 also exhibits a wide variety of effects in hematopoiesis and the immune system as an acute phase protein, whereas thymosin beta-4 regulates cell life, differentiation, proliferation/growth, migration, and motility [1,5]. (thermofisher.com)
  • Malignant cells compete with their normal counterparts for niche resources and occupancy, and disrupt normal hematopoiesis by inflicting a differentiation block, which often manifests itself as BM failure and pancytopenia. (haematologica.org)
  • Gene expression analyses, gene targeting experiments and retroviral overexpression studies in the murine bone marrow transplantation model have provided strong correlative evidence for the involvement of clustered Hox genes in normal hematopoiesis. (nih.gov)
  • Extramedullary hematopoiesis (EMH or sometimes EH) refers to hematopoiesis occurring outside of the medulla of the bone (bone marrow). (wikipedia.org)
  • Pathologic EMH can occur during adulthood when physiologic hematopoiesis can't work properly in the bone marrow and the hematopoietic stem cells (HSC) have to migrate to other tissues in order to continue with the formation of blood cellular components. (wikipedia.org)
  • During fetal development, hematopoiesis occurs mainly in the fetal liver and in the spleen followed by localization to the bone marrow. (wikipedia.org)
  • In comparison to the bone marrow, where trilineage hematopoiesis occurs, the lungs preferentially contribute to the production of platelets through a resident population of megakaryocytes. (wikipedia.org)
  • In adults, the majority of hematopoiesis occurs in the bone marrow. (wikipedia.org)
  • Extramedullary hematopoiesis (EMH) is a normal response to failure of hematopoiesis at its normal site i.e ., bone marrow. (springer.com)
  • The marrow space also contains stromal cells that support hematopoiesis including the production of cytokines, such as c-Kit ligand, that stimulate stem cells and progenitors. (nih.gov)
  • Clonal hematopoiesis may be an early precursor of leukemia and a rare bone marrow disorder known as myelodysplastic syndrome. (aacr.org)
  • Extramedullary hematopoiesis is the production of blood elements outside the bone marrow cavity. (appliedradiology.com)
  • Thereafter, the bone marrow is the primary site of hematopoiesis. (appliedradiology.com)
  • Extramedullary hematopoiesis occurs as a compensatory mechanism for abnormal hematopoiesis when normal red marrow is unable to function because of deficiency disorders or because of various pluripotent stem cell disorders. (appliedradiology.com)
  • These data for the first time demonstrate that Epo regulates the formation of bone by both direct and indirect pathways, and further demonstrates the exquisite coupling between hematopoiesis and osteopoiesis in the marrow. (sigmaaldrich.com)
  • One of the most popular hypothesesis that EMH is a physiologic, compensatory mechanism for unstable bone marrow hematopoiesis. (appliedradiology.com)
  • In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. (thefullwiki.org)
  • Lymphoid hematopoiesis is not trivial, because although lymphocytes are found in the bloodstream and their precursor originates in the bone marrow, they mainly belong to the separate lymphatic system, which interacts with the blood circulation. (intechopen.com)
  • Cyp27a1-deficient mice had significantly reduced 27HC levels, HSC mobilization, and EMH during pregnancy but normal bone marrow hematopoiesis and EMH in response to bleeding or G-CSF treatment. (jci.org)
  • CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance, which are mutations in bone marrow stem cells that give that population of cells a survival or 'clonal' advantage for growth. (clinicaltrials.gov)
  •   Adult Cutaneous extramedullary hematopoiesis is a rare cutaneous manifestation of myelofibrosis, where hematopoiesis occurs in the skin rather than the bone marrow, causing polymorphic skin lesions. (visualdx.com)
  • IL-1 plays an important role in hematopoiesis by stimulating marrow stromal cells to secrete CSFs (colony stimulating factors). (thermofisher.com)
  • However, the role of bone marrow hematopoiesis in developing cytopenia remains virtually unexplored. (omicsonline.org)
  • Thus, the bone marrow of patients with liver cirrhosis is characterized by signs of ineffective hematopoiesis and dysplastic changes of karyocytes. (omicsonline.org)
  • However, extramedullary hematopoiesis is found often in autopsy material from cases in which there is no detectable bone marrow deficiency. (annals.org)
  • The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. (haematologica.org)
  • Serial bone marrow biopsies showed normalization of trilineage hematopoiesis in patients who had a response, without increased fibrosis . (aamds.org)
  • While EMH is physiological during fetal development, pathogenic EMH can emanate when physiological haematopoiesis in the bone marrow is ineffective and haematopoietic stem cells migrate to other tissues, as is often seen in disorders of the haematopoietic system, such as thalassemia and myelofibrosis. (bmj.com)
  • Recombinant Human Thrombopoietin Treatment Promotes Hematopoiesis Recovery in Patients with Severe Aplastic Anemia Receiving Immunosuppressive Therapy," BioMed Research International , vol. 2015, Article ID 597293, 6 pages, 2015. (hindawi.com)
  • Hematopoiesis during the early stages of embryogenesis occurs in the yolk sac and subsequently in the liver. (news-medical.net)
  • Primitive hematopoiesis occurs in the yolk sac during early embryonic development. (wikipedia.org)
  • Interestingly, despite all of the evidence suggesting an essential role for Cdx genes in hematopoietic development, no significant defects in hematopoiesis have been observed in Cdx single or compound deficient mice ( 2 ⇓ ⇓ - 5 ). (pnas.org)
  • To determine whether thrombopoietin was involved in the stimulation of hematopoiesis, we irradiated mice in which thrombopoietin deficiency had been induced by homologous recombination. (irsn.fr)
  • In fetuses from conditional ESAM-knockout mice, in which ESAM was deficient specifically in HSCs or ECs, the hematopoiesis-supporting ability was also impaired in ECs derived from ESAM-null mice. (innovations-report.com)
  • To study the role of Tfr1 in hematopoiesis, we generated hematopoietic stem cell (HSC) specific Tfr1 knockout mice. (haematologica.org)
  • However this increase in uncommitted progenitors did not result in an increase in effective haematopoiesis, but rather chronically infected mice displayed signs of anaemia and thrombocytopenia. (bl.uk)
  • Primitive hematopoiesis occurs at two anatomical sites: the rostral blood island (RBI) arising from the cephalic mesoderm and the intermediate cell mass (ICM) located in the trunk, ventral to the notochord. (biologists.org)
  • Embryonic primitive hematopoiesis (yellow) starts at around 11 hours post fertilization (hpf) when hemangioblasts (which have the potential to become either endothelial vascular cells or hematopoietic cells, shown in white) appear in the anterior lateral mesoderm (ALM) and posterior lateral mesoderm (PLM), which collectively are analogous to the blood islands in the mammalian yolk sac. (biologists.org)
  • The data strongly support the hypothesis that the role of Hox genes in normal hematopoiesis is primarily at the level of hematopoietic stem cell function. (nih.gov)
  • Defining niche cells and unveiling its function have been the subject of intense study, and it is becoming increasingly clear how niche cells regulate HSCs in normal hematopoiesis. (frontiersin.org)
  • In addition, macrophages play a critical role in normal hematopoiesis. (omicsonline.org)
  • Of note, cutaneous extramedullary hematopoiesis is a normal occurrence during early embryogenesis, and it occurs until about the fifth month of gestation. (visualdx.com)
  • Cutaneous extramedullary hematopoiesis in pre-term or full-term neonates is thought to be an accentuation of a normal physiologic process. (visualdx.com)
  • These unique attributes have uncovered novel genes, cell types, and cellular behaviors that are required for normal vertebrate hematopoiesis. (rupress.org)
  • The pathways of lineage commitment during normal hematopoiesis are of great significance in order to understand the underlying events that lead to leukemia, and to the design of proper treatments for prevention and remission of the disease. (lu.se)
  • The monophyletic theory on hematopoiesis, which is widely accepted, suggests that all of the hematopoietic cells are generated on the basis of pluripotent stem cells, which become unipotential ones and differentiate into precursor cells before going on to form mature blood cells. (news-medical.net)
  • 1 Extramedullary hematopoiesis occurs in severe chronic anemia, which can arise from deficiency disorders such as vitamin B 12 or folate deficiency 2 or from disorders affecting pluripotent stem cells. (appliedradiology.com)
  • Transferrin receptor 1 (Tfr1) mediates the endocytosis of diferric transferrin in order to transport iron, and Tfr1 has been suggested to play an important role in hematopoiesis. (haematologica.org)
  • The cytokine Fms-like tyrosine kinase 3 ligand (FL) is an important regulator of hematopoiesis. (mdpi.com)
  • Transforming growth factor-beta (TGF-beta) is perhaps the most potent endogenous negative regulator of hematopoiesis. (nih.gov)
  • However, it remains unknown whether gut microbiota control immunity through regulation of hematopoiesis at primary immune sites. (caltech.edu)
  • In hematopoiesis, a process essential for growth and life maintenance for mammals, HSCs give rise to other blood cells for the organism's entire life. (innovations-report.com)
  • These results show that ESAM expressed on ECs as well as HSCs contribute to adult-type hematopoiesis. (innovations-report.com)
  • Lead author UEDA Tomoaki says, "Properties of HSCs and hematopoiesis mechanisms are not well understood because it is difficult to study hematopoiesis, especially in human fetal life. (innovations-report.com)
  • The route of hematopoiesis can be thought of as a hierarchical tree, with the rare HSCs at the top, transitioning down along the pathways as different progenitors. (lu.se)
  • The amenity of the Xenopus model to lineage tracing experiments has also contributed to the establishment of the distinct origins of embryonic (yolk sac) and adult ( HSC ) hematopoiesis, whereas the transparency of the zebrafish has allowed in vivo imaging of developing blood cells, particularly during and after the emergence of HSCs in the DA. (xenbase.org)
  • Hematopoiesis also takes place in many other tissues or organs such as the yolk sac, the aorta-gonad mesonephros (AGM) region, the spleen, and lymph nodes. (wikipedia.org)
  • A) Hematopoiesis occurs first in the yolk sac (YS) blood islands and later at the aorta-gonad mesonephros (AGM) region, placenta, and fetal liver (FL). (nih.gov)
  • Clonal hematopoiesis (CH) refers to recurrent somatic mutations in leukemia-associated genes that are commonly acquired in aging human hematopoietic stem cells. (medscape.com)
  • Hox genes in hematopoiesis and leukemogenesis. (nih.gov)
  • Given the documented role of Hox genes in hematopoiesis and leukemogenesis, we propose that Hox-dependent pathways are closely linked to the self-renewal program crucial to the origin and function of leukemic stem cells. (nih.gov)
  • To define the role of Cdx genes during embryonic hematopoiesis in a mammalian system, we examined the hematopoietic potential of Cdx -deficient mouse embryonic stem cells (ESCs) in vitro and in vivo . (pnas.org)
  • These results reveal an essential and partially redundant role for multiple Cdx genes during embryonic hematopoiesis in the mouse. (pnas.org)
  • A potential role for Cdx genes in embryonic hematopoiesis initially came from studies in zebrafish. (pnas.org)
  • This led us to hypothesize that Cdx genes may have overlapping or redundant functions during hematopoiesis, and that defects during embryonic stages of hematopoietic development may ultimately be masked by compensatory mechanisms in the adult. (pnas.org)
  • We sequenced the exome of individual hematopoietic colonies derived from 13 patients with congenital neutropenia to measure total mutation burden and performed error-corrected sequencing on a panel of 46 genes on 80 patients with congenital neutropenia to assess for clonal hematopoiesis. (bloodjournal.org)
  • On the other hand, chromosomal translocations involving the CBFA2 and CBFB genes in leukemias block hematopoiesis at later steps. (aacrjournals.org)
  • Of the six genes that were up-regulated in both hemogenic mesoderm and hemogenic endothelial fractions targeted by the reporters, LRP2, a multiligand receptor, was the only gene that had not previously been associated with hematopoiesis. (mdc-berlin.de)
  • Specifically, INTS13 regulates enhancers of genes associated with immune cell development and hematopoiesis. (wistar.org)
  • They can also migrate to the spleen and lymph nodes where hematopoiesis can occur, but to a lesser degree. (wikipedia.org)
  • 1 Extramedullary hematopoiesis mainly involves the RE system (liver, spleen, and lymph nodes) but is also known to occur in every organ of the body, including the thyroid, prostate, pericardium, kidney, and lungs. (appliedradiology.com)
  • The establishment of a clonal population may occur when a stem or progenitor cell acquires one or more somatic mutations that give it a competitive advantage in hematopoiesis over the stem/progenitor cells without these mutations. (wikipedia.org)
  • The advent of next-generation DNA sequencing has allowed for the targeted identification of somatic mutations involved in clonal hematopoiesis at the population level. (wikipedia.org)
  • Clonal hematopoiesis (CH) is an age-related condition in which somatic (acquired) genetic mutations drive oligoclonal expansion of hematopoietic cells. (harvard.edu)
  • Zebrafish are an ideal model to use to study hematopoiesis. (rupress.org)
  • Are transplantable stem cells required for adult hematopoiesis? (stembook.org)
  • Cdx1 functions redundantly with cdx4 to promote hematopoiesis in zebrafish ( 6 , 7 ). (pnas.org)
  • Does Maitake Mushroom Extract Enhance Hematopoiesis in Myelodysplastic Patients? (clinicaltrials.gov)
  • The findings suggest that disrupting this mode of intercellular communication might enhance hematopoiesis in AML patients. (sciencemag.org)
  • Clonal hematopoiesis (CH) is a precursor clonal state that confers increased risk of leukemia and occurs at an elevated rate in patients with thyroid cancer relative to other solid tumors. (medscape.com)
  • CHIP' stands for Clonal Hematopoiesis of Indeterminate Significance (1-4). (clinicaltrials.gov)
  • mTOR complex 1 plays critical roles in hematopoiesis and Pten-loss-evoked leukemogenesis. (biomedsearch.com)
  • However, the roles of the unique mTOR complexes (mTORCs) in hematopoiesis and leukemogenesis have not been adequately elucidated. (biomedsearch.com)
  • Hematopoietic stressors may contribute to leukemic transformation by increasing the mutation rate in hematopoietic stem/progenitor cells (HSPCs) and/or by promoting clonal hematopoiesis. (bloodjournal.org)
  • Recently, aging has been linked with the development of age-related clonal hematopoiesis (ARCH), defined as the gradual clonal expansion of hematopoietic stem and progenitor cells (HSPC) carrying recurrent disruptive genetic variants in individuals without a diagnosis of hematologic malignancy. (ovid.com)
  • The combination of these two ideas, that clonal hematopoiesis might be common in the elderly population and that AML evolves from pre-leukemic populations, led to the hypothesis that malignancy-associated mutations could also contribute to asymptomatic clonal hematopoiesis in healthy individuals. (wikipedia.org)
  • This view gained mechanistic support in 2012 when it was found a number of the women who showed evidence for clonal hematopoiesis through X-inactivation skew also had mutations in the hematologic-malignancy-associated gene TET2. (wikipedia.org)
  • The other main common finding is that there are many different mutations involved in clonal hematopoiesis. (wikipedia.org)
  • Clonal hematopoiesis due to mutations of TP53 is present in the majority of patients with SDS. (bloodjournal.org)
  • Conversely, clonal hematopoiesis due to mutations of CSF3R was present in patients with SCN but was not detected in healthy controls or patients with SDS. (bloodjournal.org)
  • This study demonstrates how clonal hematopoiesis (CH)-derived mutations could lead to erroneous reporting and treatment recommendations when tumor-only sequencing is employed. (mskcc.org)
  • Because most cfDNA is derived from peripheral blood cells (PBC), we hypothesized that nonmalignant mutations harbored by hematopoietic cells (clonal hematopoiesis, CH) could be a cause of false-positive plasma genotyping. (aacrjournals.org)
  • Further study of larger populations, mutations co-occurring within the same pre-leukemic clone and other risk factors (lifestyle, epigenetics, etc.), are still needed to fully elucidate the risk conferred by low-frequency clonal hematopoiesis in asymptomatic adults. (haematologica.org)
  • Acute respiratory failure due to extra-medullary hematopoiesis.Chest.1995;108:1170-1172. (appliedradiology.com)
  • This volume of Molecular Biology of Hematopoiesis is dedicated to many inter- national scientists and clinicians for their contribution to the field of Hematology/ Oncology presented at the 11th International Symposium on Molecular Biology of Hematopoiesis, which was held in Bormio, Italy, June 25-29, 1998. (springer.com)
  • The Hematopoiesis and Hematopoietic Stem Cell Biology program focuses on understanding the basic cellular and molecular mechanisms underlying the production and function of blood cells in health and disease. (nih.gov)
  • The underlying molecular pathways involved in the initiation and maintenance of hematopoiesis at different stages during embryogenesis are poorly understood. (pnas.org)
  • Despite extensive evolutionary divergence between bony fish (teleosts) and mammals, the molecular pathways governing hematopoiesis have been highly conserved. (nih.gov)
  • The sites of blood development and the molecular signals regulating hematopoiesis are conserved with mammalian systems, and zebrafish embryos are transparent, allowing for noninvasive visualization of HSC emergence, migration, and engraftment. (rupress.org)
  • The work of this thesis is aimed to further our understanding of the molecular mechanisms involved in astakine 1 induced hematopoiesis.Crayfish transglutaminase (Tgase) has been identified in the hemocytes, and is essential for the coagulation reaction. (dissertations.se)
  • We examine recent studies on Flt3 expression by hematopoietic stem cells and its potential instructive action at early stages of hematopoiesis. (mdpi.com)
  • These results suggest that embryonic olfactory bulb stem cells are not endowed with the potential to produce hematopoiesis. (csic.es)
  • We have observed that depletion of HIF-1alpha accelerates haematopoiesis in embryonic stem cells in vitro. (muni.cz)
  • These findings show that adult tissue-resident macrophages and innate-like lymphocytes develop early in fetal hematopoiesis from progenitors that emerge prior to, and apparently independently of, conventional long-term hematopoietic stem cells. (ca.gov)
  • during this time the main site of fetal hematopoiesis are liver and the spleen. (wikipedia.org)
  • During the postnatal period, the spleen is becomes a frequent site of EMH whereas, during the embryonic stages of hematopoiesis, it is only a minor factor. (wikipedia.org)
  • EMH is not commonly seen in the adrenal gland, so if it is present, it will likely also be present in other organs, most likely the spleen and liver (see Spleen - Extramedullary Hematopoiesis and Liver - Extramedullary Hematopoiesis ). (nih.gov)
  • In some vertebrates , haematopoiesis can occur wherever there is a loose stroma of connective tissue and slow blood supply, such as the gut , spleen , kidney or ovaries . (thefullwiki.org)
  • Intracranial extramedullary hematopoiesis: MR findings with pathologic correlation. (springer.com)
  • These findings will be discussed with regard to the role of macrophages in hematopoiesis and various disease states. (omicsonline.org)
  • These findings reveal that gut bacteria direct innate immune cell development via promoting hematopoiesis, contributing to our appreciation of the deep evolutionary connection between mammals and their microbiota. (caltech.edu)
  • These findings provide direct evidence that Tfr1 is essential for hematopoiesis through binding diferric transferrin to supply iron to cells. (haematologica.org)
  • Here, we discuss these recent findings, which show that an early and distinct wave of hematopoiesis occurs for all major hematopoietic lineages. (ca.gov)
  • We also discuss recent insights into B lymphocyte development and attempt to synthesize seemingly contradictory recent findings on the origins of innate-like B-1a lymphocytes during fetal hematopoiesis. (ca.gov)
  • A core liver biopsy was performed underultrasound guidance and histologic examination led to the diagnosis of extramedullary hematopoiesis (EMH) with no morphologic evidence of a malignant neoplasm. (appliedradiology.com)
  • Lemos LB, Baliga M, Benghuzzi HA, Cason Z. Nodular hematopoiesis of the liver diagnosed by fine-needle aspiration cytology. (appliedradiology.com)
  • In summary, our data demonstrate that local irradiation of the abdomen encompassing the liver leads to stimulation of hematopoiesis through a thrombopoietin-independent mechanism. (irsn.fr)
  • Major areas of interest include the basic mechanisms involved in regulating the production and terminal development of blood cells, referred to as hematopoiesis. (nih.gov)
  • Alternatively, clonal hematopoiesis may arise without a driving mutation, through mechanisms such as neutral drift in the stem cell population. (wikipedia.org)
  • We'd like to continue our research so that our achievements will elucidate the mechanisms of hematopoiesis and lead to the identification of the cause of congenital disorders of the hematopoietic system, especially the cause of genetic anemia, and the development of treatment methods. (innovations-report.com)
  • However, the molecules and mechanisms that regulate BMP/Smad signaling in hematopoiesis are largely unknown. (biologists.org)
  • Septate junction components function as upstream regulators of the Hippo signaling pathway in the lymph gland, a non-polarized organ, to control Drosophila hematopoiesis and the cellular immune response. (biologists.org)
  • Here, we will review recent studies linking clonal hematopoiesis to altered immune function, inflammation, and non-malignant diseases of aging. (onmedica.com)
  • Hemocytes (blood cells) play an important role in the immune response in invertebrates, and thus the regulation of hemocyte homeostasis (hematopoiesis) is essential for the host survival against pathogens. (dissertations.se)
  • There was high concordance between our signatures and those from embryos with defects at corresponding stages of hematopoiesis. (mdc-berlin.de)
  • Studies of hematopoiesis provide critical insights of general relevance to other areas of stem cell biology including the role of cellular interactions in development and tissue homeostasis, lineage programming and reprogramming by transcription factors, and stage- and age-specific differences in cellular phenotypes. (nih.gov)
  • Intrathoracic extramedullary hematopoiesis resembling posterior mediastinal tumor. (appliedradiology.com)
  • QIAGEN provides a broad range of assay technologies for hematopoiesis research that enables analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. (qiagen.com)
  • Moreover, a novel cysteine rich protein, Pacifastacus hematopoiesis factor (PHF), was found to be one target gene of astakine 1 in Hpt cells. (dissertations.se)
  • Hematopoiesis is the process by which blood cells are created. (news-medical.net)
  • Hematopoiesis is the process of creating new blood cells in the body. (youtube.com)
  • Having clonal hematopoiesis has been linked to a more than 10-fold increased risk of developing a blood cancer, though the overall likelihood is still low. (wikipedia.org)
  • B) Hematopoiesis in each location favors the production of specific blood lineages. (nih.gov)
  • If such a mutation provides an advantage for one stem cell over the others, the progeny of this genetically distinct stem cell might come to dominate blood cell production, a phenomenon known as clonal hematopoiesis. (aacr.org)
  • Of note, clonal hematopoiesis would have been a silent condition were it not recognized via DNA sequencing of blood cells, because it is not associated with symptoms or abnormalities in conventional laboratory tests. (aacr.org)
  • Fortunately, the chance for these blood cancers to appear in people with clonal hematopoiesis may be 1 percent or less per year. (aacr.org)
  • Fig. 1: Deep sequencing of longitudinal samples reveals the clonal architecture within the peripheral blood of an elderly subject with age-related clonal hematopoiesis. (nature.com)
  • Hematopoiesis is a complex but precisely regulated process that gives rise to blood cells of all lineages. (plymouth.ac.uk)
  • Hematopoiesis needs to be maintained throughout life to supply blood cells on various demands, such as infection, inflammation, blood loss, or hypoxia. (frontiersin.org)
  • Extramedullary hematopoiesis (EMH) is induced during pregnancy to support rapid expansion of maternal blood volume. (jci.org)
  • The production of blood cells is called hematopoiesis. (fondationleducq.org)
  • It is thought that the resulting subpopulation of blood cells is "clonally" derived from a single founding cell and is therefore made of genetic "clones" of the founder.Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic (blood) diseases. (fondationleducq.org)
  • Hematopoiesis, the dynamic process of blood cell development, is regulated by the activity of the bone morphogenetic protein (BMP) signaling pathway and by many transcription factors. (biologists.org)
  • Hematopoiesis is the process that gives rise to all types of blood cells. (biologists.org)
  • The results of the analyses demonstrated hematopoiesis inhibition manifested by a decrease in peripheral blood cellularity and an increase in the frequency of cytopenia in all blood cell lines (leukocytes, including lymphocytes, monocytes, neutrophiles, as well as platelets and erythrocytes). (duke.edu)
  • Subsequently, using mixed BM chimeras, we established that IFNγ signalling and TNF signalling pathways converge to induce an expansion of BM T cells, suggesting that both cytokines are required to drive the development of CD4+ T cells with the potential to cause alterations in haematopoiesis and haematological dysfunction in the periphery. (bl.uk)
  • Discovery of novel PAX-SIX-EYA-DACH and GATA network interactions in Drosophila hematopoiesis reveal that human SIX proteins can associate with GATA1, stimulate GATA1-dependent transcription and enhance human erythropoiesis in vitro . (biologists.org)
  • To determine whether extracellular DEK required nuclear function to regulate hematopoiesis, we utilized 2 mutant forms of DEK: one that lacked its nuclear translocation signal and one that lacked DNA-binding ability. (jci.org)
  • Extracellular DEK does not require its nuclear function to regulate hematopoiesis. (jci.org)
  • Interestingly, targeting other Integrator subunits also leads to defects in smad5 RNA splicing and arrested hematopoiesis, suggesting that the Ints proteins function as a complex to regulate the BMP pathway during hematopoiesis. (biologists.org)
  • Clonal hematopoiesis may occur in people who are completely healthy but has also been found in people with hematologic diseases. (wikipedia.org)
  • If the loss of RBCs becomes severe, hematopoiesis will occur in the extramedullary spaces outside the bone. (wikipedia.org)
  • Extramedullary hematopoiesis (EMH) can occur in various tissues, including the adrenal cortex and medulla. (nih.gov)