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.
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.
An abnormal hemoglobin resulting from the substitution of valine for glutamic acid at position 6 of the beta chain of the globin moiety. The heterozygous state results in sickle cell trait, the homozygous in sickle cell anemia.
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
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.
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.
Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing HEMOGLOBIN whose function is to transport OXYGEN.
Hemoglobins characterized by structural alterations within the molecule. The alteration can be either absence, addition or substitution of one or more amino acids in the globin part of the molecule at selected positions in the polypeptide chains.
The series of cells in the red blood cell lineage at various stages of differentiation.
Normal adult human hemoglobin. The globin moiety consists of two alpha and two beta chains.
One of the sickle cell disorders characterized by the presence of both hemoglobin S and hemoglobin C. It is similar to, but less severe than sickle cell anemia.
A superfamily of proteins containing the globin fold which is composed of 6-8 alpha helices arranged in a characterstic HEME enclosing structure.
Progenitor cells from which all blood cells derive.
A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.
Immature ERYTHROCYTES. In humans, these are ERYTHROID CELLS that have just undergone extrusion of their CELL NUCLEUS. They still contain some organelles that gradually decrease in number as the cells mature. RIBOSOMES are last to disappear. Certain staining techniques cause components of the ribosomes to precipitate into characteristic "reticulum" (not the same as the ENDOPLASMIC RETICULUM), hence the name reticulocytes.
A disease characterized by compensated hemolysis with a normal hemoglobin level or a mild to moderate anemia. There may be intermittent abdominal discomfort, splenomegaly, and slight jaundice.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Agents used to prevent or reverse the pathological events leading to sickling of erythrocytes in sickle cell conditions.
ERYTHROCYTE size and HEMOGLOBIN content or concentration, usually derived from ERYTHROCYTE COUNT; BLOOD hemoglobin concentration; and HEMATOCRIT. The indices include the mean corpuscular volume (MCV), the mean corpuscular hemoglobin (MCH), and the mean corpuscular hemoglobin concentration (MCHC).
A compound formed by the combination of hemoglobin and oxygen. It is a complex in which the oxygen is bound directly to the iron without causing a change from the ferrous to the ferric state.
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.
A plant genus of the family LAURACEAE. Members contain laurotetanine and other APORPHINES.
The major component of hemoglobin in the fetus. This HEMOGLOBIN has two alpha and two gamma polypeptide subunits in comparison to normal adult hemoglobin, which has two alpha and two beta polypeptide subunits. Fetal hemoglobin concentrations can be elevated (usually above 0.5%) in children and adults affected by LEUKEMIA and several types of ANEMIA.
Oxygen-carrying RED BLOOD CELLS in mammalian blood that are abnormal in structure or function.
A disorder characterized by reduced synthesis of the beta chains of hemoglobin. There is retardation of hemoglobin A synthesis in the heterozygous form (thalassemia minor), which is asymptomatic, while in the homozygous form (thalassemia major, Cooley's anemia, Mediterranean anemia, erythroblastic anemia), which can result in severe complications and even death, hemoglobin A synthesis is absent.
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.
A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.
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.
The volume of packed RED BLOOD CELLS in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, ANEMIA shows a low value; POLYCYTHEMIA, a high value.
The major sialoglycoprotein of the human erythrocyte membrane. It consists of at least two sialoglycopeptides and is composed of 60% carbohydrate including sialic acid and 40% protein. It is involved in a number of different biological activities including the binding of MN blood groups, influenza viruses, kidney bean phytohemagglutinin, and wheat germ agglutinin.
The number of RED BLOOD CELLS per unit volume in a sample of venous BLOOD.
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.
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.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.
An increase in the total red cell mass of the blood. (Dorland, 27th ed)
An increase in circulating RETICULOCYTES, which is among the simplest and most reliable signs of accelerated ERYTHROCYTE production. Reticulocytosis occurs during active BLOOD regeneration (stimulation of red bone marrow) and in certain types of ANEMIA, particularly CONGENITAL HEMOLYTIC ANEMIA.
Cell surface proteins that bind erythropoietin with high affinity and trigger intracellular changes influencing the behavior of cells.
A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia.
An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.
A commonly occurring abnormal hemoglobin in which lysine replaces a glutamic acid residue at the sixth position of the beta chains. It results in reduced plasticity of erythrocytes.
Members of the beta-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 11. They include epsilon-globin, gamma-globin, delta-globin and beta-globin. There is also a pseudogene of beta (theta-beta) in the gene cluster. Adult HEMOGLOBIN is comprised of two ALPHA-GLOBIN chains and two beta-globin chains.
A group of transcription factors that were originally described as being specific to ERYTHROID CELLS.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.
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).
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.
Members of the alpha-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 16. They include zeta-globin and alpha-globin. There are also pseudogenes of zeta (theta-zeta) and alpha (theta-alpha) in the cluster. Adult HEMOGLOBIN is comprised of 2 alpha-globin chains and 2 beta-globin chains.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
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 family of intracellular CYSTEINE ENDOPEPTIDASES that play a role in regulating INFLAMMATION and APOPTOSIS. They specifically cleave peptides at a CYSTEINE amino acid that follows an ASPARTIC ACID residue. Caspases are activated by proteolytic cleavage of a precursor form to yield large and small subunits that form the enzyme. Since the cleavage site within precursors matches the specificity of caspases, sequential activation of precursors by activated caspases can occur.
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.
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 large group of proteins that control APOPTOSIS. This family of proteins includes many ONCOGENE PROTEINS as well as a wide variety of classes of INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS such as CASPASES.
Established cell cultures that have the potential to propagate indefinitely.
Suppression of erythropoiesis with little or no abnormality of leukocyte or platelet production.
A short pro-domain caspase that plays an effector role in APOPTOSIS. It is activated by INITIATOR CASPASES such as CASPASE 9. Isoforms of this protein exist due to multiple alternative splicing of its MESSENGER RNA.
An abnormal hemoglobin that results from the substitution of lysine for glutamic acid at position 26 of the beta chain. It is most frequently observed in southeast Asian populations.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Minor hemoglobin components of human erythrocytes designated A1a, A1b, and A1c. Hemoglobin A1c is most important since its sugar moiety is glucose covalently bound to the terminal amino acid of the beta chain. Since normal glycohemoglobin concentrations exclude marked blood glucose fluctuations over the preceding three to four weeks, the concentration of glycosylated hemoglobin A is a more reliable index of the blood sugar average over a long period of time.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
The senescence of RED BLOOD CELLS. Lacking the organelles that make protein synthesis possible, the mature erythrocyte is incapable of self-repair, reproduction, and carrying out certain functions performed by other cells. This limits the average life span of an erythrocyte to 120 days.
An adult hemoglobin component normally present in hemolysates from human erythrocytes in concentrations of about 3%. The hemoglobin is composed of two alpha chains and two delta chains. The percentage of HbA2 varies in some hematologic disorders, but is about double in beta-thalassemia.
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
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.
Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released.
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 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.
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).
Proteins prepared by recombinant DNA technology.
Anemia characterized by the presence of erythroblasts containing excessive deposits of iron in the marrow.
Unstable isotopes of iron that decay or disintegrate emitting radiation. Fe atoms with atomic weights 52, 53, 55, and 59-61 are radioactive iron isotopes.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
An encapsulated lymphatic organ through which venous blood filters.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A conserved class of proteins that control APOPTOSIS in both VERTEBRATES and INVERTEBRATES. IAP proteins interact with and inhibit CASPASES, and they function as ANTI-APOPTOTIC PROTEINS. The protein class is defined by an approximately 80-amino acid motif called the baculoviral inhibitor of apoptosis repeat.
Very large BONE MARROW CELLS which release mature BLOOD PLATELETS.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
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.
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
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.
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 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.
A familial disorder characterized by ANEMIA with multinuclear ERYTHROBLASTS, karyorrhexis, asynchrony of nuclear and cytoplasmic maturation, and various nuclear abnormalities of bone marrow erythrocyte precursors (ERYTHROID PRECURSOR CELLS). Type II is the most common of the 3 types; it is often referred to as HEMPAS, based on the Hereditary Erythroblast Multinuclearity with Positive Acidified Serum test.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
An in situ method for detecting areas of DNA which are nicked during APOPTOSIS. Terminal deoxynucleotidyl transferase is used to add labeled dUTP, in a template-independent manner, to the 3 prime OH ends of either single- or double-stranded DNA. The terminal deoxynucleotidyl transferase nick end labeling, or TUNEL, assay labels apoptosis on a single-cell level, making it more sensitive than agarose gel electrophoresis for analysis of DNA FRAGMENTATION.
A group of inherited disorders characterized by structural alterations within the hemoglobin molecule.
A cell line derived from cultured tumor cells.
A class of large neuroglial (macroglial) cells in the central nervous system. Oligodendroglia may be called interfascicular, perivascular, or perineuronal (not the same as SATELLITE CELLS, PERINEURONAL of GANGLIA) according to their location. They form the insulating MYELIN SHEATH of axons in the central nervous system.
Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS.
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.
Leukemia induced experimentally in animals by exposure to leukemogenic agents, such as VIRUSES; RADIATION; or by TRANSPLANTATION of leukemic tissues.
A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The rate dynamics in chemical or physical systems.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A family of hemoglobin-like proteins found in BACTERIA; PLANTS; and unicellular eukaryotes. Truncated hemoglobins are distantly related to vertebrate hemoglobins and are typically shorter than vertebrate hemoglobins by 20-40 residues.
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.
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.
The external genitalia of the female. It includes the CLITORIS, the labia, the vestibule, and its glands.
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.
The semi-permeable outer structure of a red blood cell. It is known as a red cell 'ghost' after HEMOLYSIS.
An inhibitor of apoptosis protein that is translated by a rare cap-independent mechanism. It blocks caspase-mediated cellular destruction by inhibiting CASPASE 3; CASPASE 7; and CASPASE 9.
Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
A single-pass type I membrane protein. It is cleaved by AMYLOID PRECURSOR PROTEIN SECRETASES to produce peptides of varying amino acid lengths. A 39-42 amino acid peptide, AMYLOID BETA-PEPTIDES is a principal component of the extracellular amyloid in SENILE PLAQUES.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Measurement of hemoglobin concentration in blood.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
Endogenous and exogenous compounds and that either inhibit CASPASES or prevent their activation.
An APOPTOSIS-regulating protein that is structurally related to CASPASE 8 and competes with CASPASE 8 for binding to FAS ASSOCIATED DEATH DOMAIN PROTEIN. Two forms of CASP8 and FADD-like apoptosis regulating protein exist, a long form containing a caspase-like enzymatically inactive domain and a short form which lacks the caspase-like domain.
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.
A long pro-domain caspase that contains a caspase recruitment domain in its pro-domain region. Caspase 9 is activated during cell stress by mitochondria-derived proapoptotic factors and by CARD SIGNALING ADAPTOR PROTEINS such as APOPTOTIC PROTEASE-ACTIVATING FACTOR 1. It activates APOPTOSIS by cleaving and activating EFFECTOR CASPASES.
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.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
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.
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.)
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
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.
A long pro-domain caspase that contains a death effector domain in its pro-domain region. Caspase 8 plays a role in APOPTOSIS by cleaving and activating EFFECTOR CASPASES. Activation of this enzyme can occur via the interaction of its N-terminal death effector domain with DEATH DOMAIN RECEPTOR SIGNALING ADAPTOR PROTEINS.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Physiologically inactive substances that can be converted to active enzymes.
A transmembrane protein belonging to the tumor necrosis factor superfamily that was originally discovered on cells of the lymphoid-myeloid lineage, including activated T-LYMPHOCYTES and NATURAL KILLER CELLS. It plays an important role in immune homeostasis and cell-mediated toxicity by binding to the FAS RECEPTOR and triggering APOPTOSIS.
Members of the beta-globin family. In humans, two non-allelic types of gamma-globin - A gamma and G gamma are encoded in the beta-globin gene cluster on CHROMOSOME 11. Two gamma-globin chains combine with two ZETA-GLOBIN chains to form the embryonic hemoglobin Portland. Fetal HEMOGLOBIN F is formed from two gamma-globin chains combined with two ALPHA-GLOBIN chains.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Substances that are used in place of blood, for example, as an alternative to BLOOD TRANSFUSIONS after blood loss to restore BLOOD VOLUME and oxygen-carrying capacity to the blood circulation, or to perfuse isolated organs.
A group of abnormal hemoglobins with similar electrophoretic characteristics. They have faster electrophoretic mobility and different amino acid substitutions in either the alpha or beta chains than normal adult hemoglobin. Some of the variants produce hematologic abnormalities, others result in no clinical disorders.
Chloro(7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-dipropanoato(4-)-N(21),N(22),N(23),N(24)) ferrate(2-) dihydrogen.
Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
An abnormal hemoglobin composed of four beta chains. It is caused by the reduced synthesis of the alpha chain. This abnormality results in ALPHA-THALASSEMIA.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
Transport proteins that carry specific substances in the blood or across cell membranes.
A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.
Glycoproteins found on the membrane or surface of cells.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
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.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A highly anionic organic phosphate which is present in human red blood cells at about the same molar ratio as hemoglobin. It binds to deoxyhemoglobin but not the oxygenated form, therefore diminishing the oxygen affinity of hemoglobin. This is essential in enabling hemoglobin to unload oxygen in tissue capillaries. It is also an intermediate in the conversion of 3-phosphoglycerate to 2-phosphoglycerate by phosphoglycerate mutase (EC 5.4.2.1). (From Stryer Biochemistry, 4th ed, p160; Enzyme Nomenclature, 1992, p508)
Exogenous and endogenous compounds which inhibit CYSTEINE ENDOPEPTIDASES.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A protein of the annexin family isolated from human PLACENTA and other tissues. It inhibits cytosolic PHOSPHOLIPASE A2, and displays anticoagulant activity.
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.
RNA transcripts of the DNA that are in some unfinished stage of post-transcriptional processing (RNA PROCESSING, POST-TRANSCRIPTIONAL) required for function. RNA precursors may undergo several steps of RNA SPLICING during which the phosphodiester bonds at exon-intron boundaries are cleaved and the introns are excised. Consequently a new bond is formed between the ends of the exons. Resulting mature RNAs can then be used; for example, mature mRNA (RNA, MESSENGER) is used as a template for protein production.
Inhibitors of SERINE ENDOPEPTIDASES and sulfhydryl group-containing enzymes. They act as alkylating agents and are known to interfere in the translation process.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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)
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A type VI intermediate filament protein expressed mostly in nerve cells where it is associated with the survival, renewal and mitogen-stimulated proliferation of neural progenitor cells.
Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
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 parts of a macromolecule that directly participate in its specific combination with another molecule.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
An essential GATA transcription factor that is expressed primarily in HEMATOPOIETIC STEM CELLS.
A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8)
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
... by promoting their survival through protecting these cells from apoptosis, or cell death. Erythropoietin is the primary ... involved in the development of erythroid lineage from multipotent progenitors. The burst-forming unit-erythroid (BFU-E) cells ... Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in ... Risk increases when EPO treatment raises hemoglobin levels over 11 g/dL to 12 g/dL: this is to be avoided. rhEPO has been used ...
Primary role of EpoR is to promote proliferation of erythroid progenitor cells and rescue erythroid progenitors from cell death ... "Synthesis of haemoglobin in relation to the maturation of erythroid cells". Nature. 196 (4852): 347-50. doi:10.1038/196347a0. ... "Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction". Cell ... "Macrocytosis Resulting from Early Denucleation of Erythroid Precursors". Blood. 24 (5): 582-93. doi:10.1182/blood.V24.5.582.582 ...
... cell cultures of senescent human umbilical vein endothelial cells have shown that both fisetin and quercetin induce apoptosis ... February 26, 1998). "Expression of Bcl-x in erythroid precursors from patients with polycythemia vera". New England Journal of ... Because iron metabolism and incorporation into hemoglobin occurs inside the mitochondria, Bcl-xL was suggested to play ... AF, Schott (1995). "Bcl-XL protects cancer cells from p53-mediated apoptosis". Oncogene. 11 (7): 1389-1394. PMID 7478561. ...
T-cells are activated and more prone to apoptosis without KLF2, suggesting that KLF2 regulates T-cell quiescence and survival. ... but it is also expressed temporally during embryogenesis in erythroid cells, endothelium, lymphoid cells, the spleen, and white ... Hemoglobin F) to adult hemoglobin (Hemoglobin A) gene expression by binding to highly conserved CACCC domains. EKLF ablation in ... natriuretic precursor peptide C), KLF2 has a vasodilatory effect KLF2 also inhibits VEGFR2 (VEGF receptor 2) expression, having ...
In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so about 1% of human red blood cells break ... Erythroid hyperplasia with accelerated production of red cells, reflected by reticulocytosis, and slight macrocytosis in ... Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia) ... Abnormal and accelerated destruction of red cells and, in some anemias, their precursors ...
"5 aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells". Cell ... Gardener, L.C.; Cox, T.M. (1988). "Biosynthesis of heme in immature erythroid cells". The Journal of Biological Chemistry. 263 ... Being a precursor of a photosensitizer, 5ALA is also used as an add-on agent for photodynamic therapy. In contrast to larger ... Biliverdin and Bilirubin are potent anti oxidants and regulate important biological processes like inflammation, apoptosis, ...
In vivo the switch of fetal to adult hemoglobin was observed after infusion of nucleated erythroid precursors derived from ... The activity of the conditioned medium correlates directly with radiation-induced feeder cell apoptosis. Thus, conditional ... human iPS cell-derived myeloid cell lines as unlimited cell source for dendritic cell-like antigen-presenting cells". Gene ... "Human Somatic Cell Nuclear Transfer Using Adult Cells". Cell Stem Cell. 14 (6): 777-780. doi:10.1016/j.stem.2014.03.015. PMID ...
August 2006). "Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo". The Journal of ... June 2005). "Podocalyxin is a CD34-related marker of murine hematopoietic stem cells and embryonic erythroid cells". Blood. 105 ... "Mediation of apoptosis and proliferation of human embryonic stem cells by sphingosine-1-phosphate". Stem Cells and Development ... TdT telomerase reverse transcriptase electrophoretic pattern of hemoglobin Thrombomucin Thy-1 Tra-1-60 TWIST1 VEGFR-2 vimentin ...
Knocking-down lincRNA-EPS in mouse inhibited differentiation and marketed apoptosis of erythroid precursors, while its ectopic ... Col-I1+ cells noticed in this model had been triggered by raises in this type of cell loss of life. To check this speculation ... indicated that lincRNA-EPS is certainly extremely induced in erythroid precursors if they begin synthesizing hemoglobin and ... LncRNAs involved with erythroid differentiation The initial lncRNA to become related to reddish colored bloodstream cells was ...
Studies on marrow erythroid precursors in the beta-thalassemias have already shown accelerated programmed cell death and ... The unusual pathobiology of hemoglobin constant spring red blood cells BLOOD Schrier, S. L., Bunyaratvej, A., KHUHAPINANT, A., ... it seemed reasonable that oxidant damage to thalassemic erythroid precursors would cause their accelerated apoptosis and ... The loss of GMPs is likely due to increased apoptosis and increased phagocytosis, the latter due to the up-regulation of cell ...
... in erythroid culture compared to HBG1/2 promoter-edited cells. Increased production of fetal hemoglobin can be beneficial to ... Notably, editing HBG1/2 promoters upregulated fetal hemoglobin with superior repopulation of red blood cell precursors as ... at the BCL11Ae site had lower productive editing rates compared to other lineages and showed increased level of apoptosis, or ... In these experiments, NBSGW mice received an infusion of human CD34+ cells which had been edited either at the BCL11A erythroid ...
... but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and ... erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large ... Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe ... also known as sickle cell disease. Sickle cell anemia is characterized by abnormally shaped red cells resulting in chronic ...
We recorded hemoglobin values upon admission and throughout the first week of hospital stay in a consecutive cohort of septic ... While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], ... More than 20 % of them had hemoglobin levels less than 10g/dL on admission, a rate that was doubled during the first week of ... To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) ...
... of reticulocytes released from the bone marrow into the circulation and reduces apoptosis among late erythroid precursors, ... The 390 patent also provides cell targeting of drugs wherein the targeted drug is only released in cells infected with a ... Following INF-α/RBV initiation, subjects with new-onset anemia (hemoglobin ≦10 g/dL or ≧2 g/dL decrease in hemoglobin) or a ... Gogu SR, Beckman BS, Wilson RB, et al., "Inhbitory Effects of Zidovudine in Erythroid Progenitor Cells: Reversal with a ...
In addition, we show that SCF induces Btk to interact with TNF-related apoptosis-inducing ligand (TRAIL)-receptor 1 and that ... and stem cell factor (SCF). In addition to qualitative regulation of signaling pathways, quantitative control may be essential ... As a result, expansion of erythroid progenitors lacking Btk is impaired at limiting concentrations of Epo and SCF. ... to control appropriate cell numbers in peripheral blood. We demonstrate that Brutons tyrosine kinase (Btk) is able to ...
EPO acts primarily on these cells by stimulating cell division and maturation as well as inhibiting apoptosis.[7] Tissue ... EPO stimulates the proliferation and maturation of erythroid precursors in the bone marrow. The earliest progenitor form that ... hypoxia triggers endogenous EPO production when hemoglobin (Hb) falls below 12 g/dL. [8,9] When hypoxia resolves, EPO ... The anemia is mainly attributed to bone marrow replacement by lymphoma cells or inadequate erythropoietin (EPO) production ...
... causes cell death in Gpx4-deficient erythroid progenitor cells. Erythroid cells were differentiated in vitro from Gpx4F/F and ... and bone marrow erythroid progenitors (CD71+/TER119+). Red blood cell counts (B), hemoglobin levels (C), and hematocrit (D) are ... Apoptosis and necroptosis (right) are mainly regulated via TNFR1 signaling. Upon TNF binding, TNFR1 undergoes a conformational ... DTT supplementation rescues cell death in erythroid cells (F) and restores caspase 8 cleavage upon TNF-α stimulation (G). DTT ...
... loss of AHSP reduced the lifespan of circulating red blood cells and also caused increased apoptosis of erythroid precursors. ... Molecular mechanisms of AHSP-mediated stabilization of hemoglobin. Cell. In press.. *Fessas, P. Inclusions of hemoglobin ... C-E) Detection of apoptosis in erythroid precursors. Spleen sections were stained for the erythroid surface marker Ter119 ( ... Several findings indicate that mechanisms to neutralize free α-Hb exist in erythroid cells. First, erythroid precursors contain ...
Hemoglobin Subunit Beta, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human ... but in sickle cell anemia, the abnormal hemoglobin (called Hb S) causes red blood cells to become stiff. They are C-shaped and ... erythroid hyperplasia of the bone marrow with increased numbers of multinucleate red cell precursors, and the presence of large ... Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe ...
Importantly, GTE possesses antioxidant, free radical scavenging, metal-chelating, anti-hemolysis properties in cell cultures, ... which are beneficial for cell functions and health. ... The abnormal erythroid precursors are driven into apoptosis ... The spleen is an organ containing some of the RE cells that function to destroy RBC hemoglobin by macrophages and store the ... Huh7 cells = human hepatocellular carcinoma cells, RBC = red blood cells, RINm5F cells = rat insulinoma cells, ROS = reactive ...
Treating affected cells with an inhibitor of heme synthesis improves erythroid cell output in cell culture. Thus, blocking heme ... A normal adult makes 2.4 × 106 red blood cells per second; each cell contains 270 × 106 hemoglobin molecules; each molecule ... Erythroid differentiation is diagrammed in Fig. 1A. Under the influence of erythropoietin, early erythroid precursors [CFU-E ( ... How excess heme induces cell death is less certain, but this likely involves both ferroptosis and apoptosis. Ferroptosis is a ...
Up-Regulation , K562 Cells , Cell Line , Hemoglobins , Anemia, Sickle Cell , beta-Thalassemia ... apoptosis, and cancer. Recent studies indicate that mir-210 is overexpressed into erythroid linage during the differentiation ... of hematopoietic precursor. The main goal of the present study is to investigate the influence of mir-210 on the pattern of ... Apoptosis was assessed by flowcytometry after 48 h cell treatment in the presence of IC50 dose. Doubling time of K562 cells was ...
Ineffective erythropoiesis results from apoptosis of erythroid precursors and limited erythroid differentiation. Therefore, ... Transfuse red blood cells to a goal hemoglobin of 8-9 g/dL Use filtered RBCs or leukocyte-depleted blood 5-12 mL/kg/dose ... patients do not have anemia and have a normal mean cell volume (MCV) and mean corpuscular hemoglobin concentration (MCHC); ... Normal adult hemoglobin (hemoglobin A) is made of a pair of alpha globin chains and a pair of beta globin chains. A reduction ...
... with HZ or treatment with low-micromolar HNE inhibited growth of erythroid cells interfering with cell cycle without apoptosis ... expression and the impaired cell cycle activity decreased the production of cells expressing glycophorin-A and hemoglobin. ... were due to the transfer of HNE to differentiating human erythroid precursors. Erythropoiesis was inhibited by transferred HNE ... The resul was decreased expression of cyclin A and D2 retarded cell cycle progression in erythroid cells and the K562 cell line ...
... by promoting their survival through protecting these cells from apoptosis, or cell death. Erythropoietin is the primary ... involved in the development of erythroid lineage from multipotent progenitors. The burst-forming unit-erythroid (BFU-E) cells ... Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in ... Risk increases when EPO treatment raises hemoglobin levels over 11 g/dL to 12 g/dL: this is to be avoided. rhEPO has been used ...
... that is critical for the survival of early erythroid precursors (CFU-E/proerythroblasts) and demonstrated that it exports ... Abkowitzs research is hematopoietic stem cell (HSC) physiology. HSCs, the parent cells that establish and maintain blood cell ... leading to cell apoptosis, so that a tight balance between heme synthesis and heme use is required. Flvcr-/- mice die during ... as well as myoglobin and hemoglobin. It is also a transcriptional and translational regulator of globin synthesis (and thus ...
... and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and ... Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, ... E. J. Houwerzijl, H. W. Pol, N. R. Blom, J. J. van der Want, J. T. de Wolf, and E. Vellenga, "Erythroid precursors from ... overexpression is inversely correlated to hemoglobin and survival, as it favors Fas-mediated- and TNF-related apoptosis- ...
"Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells," Cell ... are characterized by developing anemia with reduced matured erythrocytes and compensatory expansion of erythroid precursors. ... L. Luo, A. M. Lu, Y. Wang et al., "Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by ... elevating hemoglobin level and red cell volume [6], improving blood volume [7], promoting blood flow rate, enhancing capillary ...
Iron acquisition by developing erythroid cells is necessary to produce hemoglobin, which allows red blood cells to deliver ... Tfr2 is highly expressed in liver hepatocytes and erythroid precursor cells, and can facilitate Tf-bound iron entry in vitro, ... The injection of iron-dextran at the 1 cell-stage rescued the hemoglobin defect in cia embryos, showing that loss of tfr1a ... Tfr1-/- mice also showed neurologic abnormalities, including kinking of their neural tubes and increased neuronal apoptosis. In ...
Cell culture and transfection. Human embryonic kidney (HEK) 293T cells (ATCC #CRL-11268) were cultured in Dulbeccos modified ... The bone marrow is normocellular, but erythroid precursors are absent or their numbers markedly decreased, because their ... and elevated hemoglobin F after 6 months of age are observed in most patients; an increase in eADA may be the only ... progenitors are unable to differentiate and are prone to apoptosis. Laboratory findings such as increased mean corpuscular ...
... the first morphologically recognizable erythroid precursor is the pronormoblast. This cell can undergo four to five cell ... In mammals, O2 is transported to tissues bound to the hemoglobin contained within circulating red cells. The mature red cell is ... undergo programmed cell death (. apoptosis). The regulated process of red cell production is erythropoiesis, and its key ... The erythron is a dynamic organ made up of a rapidly proliferating pool of marrow erythroid precursor cells and a large mass of ...
32 Transferrin receptors are present on most cells but are most dense on erythroid precursors. Each transferrin receptor can ... These trials randomized patients to either higher "normal-range" hemoglobin targets or to lower target hemoglobin levels. ... Pure red cell aplasia induced only by intravenous administration of recombinant human erythropoietin. Acta Haematol 2011; 126: ... STAT5 was found to inhibit apoptosis through the early induction of an antiapoptotic gene, Bcl-xL.26 ...
Production of β‐globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 ... High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 ... Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia ... A combined approach for β-thalassemia based on gene therapy-mediated adult hemoglobin (HbA) production and fetal hemoglobin ( ...
... programmed cell death) in red cell precursors, as well as to acquired defects during the life of the adult red cell. In our ... sickle mice that exclusively make human sickle hemoglobin. Most PS-exposing sickle cells are found in the low (d,1.08) or high ... Increased PS exposure was also found on erythroid precursors in murine bone marrow and spleen. Our studies on the survival of ... While PS exposure has been recognized as an early step in apoptosis, the mechanisms that lead to this exposure have not been ...
MDSs are clonal disorders of myeloid stem cells. ... of cells be present in two or more cell lineages. This is often ... Megaloblastoid erythroid precursors with nuclear irregularities and a multinucleated erythroid precursor. View Media Gallery ... However, in many cases of MDS, there is an increase in apoptosis among bone marrow precursors, which accounts for the ... Cytopenias are defined as a hemoglobin level below 10 g/dL, an absolute neutrophil count of less than 1,800/μL (see the ...
Red cell structure,Red cell functions,Red cell metabolic pathways,anaerobic glycolytic pathway,pentose phosphate pathway,hexose ... Download Overview of Red Cell Enzymes, Metabolic Pathways, 2,3 DPG & Oxygen Dissociation Curve by HEM for Medical, ... Hemoglobins Methemoglobin Sulfhemoglobin Carboxyhemoglobin Erythropoiesis Red Blood Cell Maturation Erythroid Progenitor Cells ... Cycle stem cells regenerative medicine genetics epigenetics cell injury cell death reversible cell injury necrosis apoptosis ...
Age Hemoglobin (g/dL Mean corpuscular volume (fL) Mean Lower limita Mean Lower limita Birth (cord blood) 16.5 13.5 108 98 1-3 ... elevated fetal hemoglobin (HbF) and adenosine deaminase (ADA) levels and a normocellular marrow with a paucity of erythroid ... Pure Red Cell Aplasia. Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia that results from defective ... precursors. About 30% of patients have associated anomalies such as short stature, dysmorphic facies, skeletal abnormalities (e ...
... apoptosis, and GDF11 in erythroid precursors. ... leading to a major reduction of red cell production.3,4 In ... Identification of TWSG1 as a second novel erythroid regulator of hepcidin expression in murine and human cells. Blood 2009;114( ... β-Thalassemias are monogenic diseases characterized by the lack or reduction of the hemoglobin β-globin chain expression ... This is likely the case because ex vivo studies confirm that EPO induces ERFE in human erythroid precursors. However, no assay ...
  • Most of them had been targeted by important erythroid transcription elements, such as for example GATA1, TAL1, or KLF1, highly supporting their functions during erythropoiesis. (cylch.org)
  • Their deposition leads to a vast increase in erythroid apoptosis that in turn causes ineffective erythropoiesis and severe microcytic hypochromic anemia. (proteopedia.org)
  • The anemia is mainly attributed to bone marrow replacement by lymphoma cells or inadequate erythropoietin (EPO) production which leads to suppressed erythropoiesis. (mjhid.org)
  • Loss of Gpx4 in hematopoietic cells induces anemia that is compensated by increased erythropoiesis. (nih.gov)
  • However, why erythropoiesis is severely affected, whereas other lineages, such as granulocytes and lymphocytes, as well as nonhematopoietic cells, function appropriately, is difficult to reconcile with this hypothesis. (sciencemag.org)
  • Other effects, such as inhibition of erythropoiesis, were due to the transfer of HNE to differentiating human erythroid precursors. (biomedcentral.com)
  • Erythropoiesis was inhibited by transferred HNE via blockage of cell cycle and the down-regulation of protein expression of crucial receptors (erythropoietinR, transferrinR and stem-cell-factorR). (biomedcentral.com)
  • In human bone marrow (BM) the erythroblastic island (EI) is the elementary unit of erythropoiesis in which a central macrophage (MAC) is surrounded by differentiating erythroid cells. (biomedcentral.com)
  • Following HZ/HNE treatment, two critical proteins in cell cycle regulation, p53 and p21, were increased and the retinoblastoma protein, central regulator of G1-to-S-phase transition, was consequently hypophosphorylated, while GATA-1, master transcription factor in erythropoiesis was reduced. (biomedcentral.com)
  • In conclusion, present data confirm the inhibitory role of HZ, identify HNE as one HZ-generated inhibitory molecule and describe molecular targets of HNE in erythroid progenitors possibly involved in erythropoiesis inhibition in malaria anemia. (biomedcentral.com)
  • More broadly, she is interested in understanding the coordinate molecular regulation of heme and globin synthesis as primary erythroid progenitor cells mature, and how dyscoordination might lead to ineffective erythropoiesis in MDS and other disorders. (uw.edu)
  • it stimulates red blood cell production (erythropoiesis) in the bone marrow. (wikipedia.org)
  • Exogenous erythropoietin, recombinant human erythropoietin (rhEPO), is produced by recombinant DNA technology in cell culture and are collectively called erythropoiesis-stimulating agents (ESA): two examples are epoetin alfa and epoetin beta. (wikipedia.org)
  • Erythropoietin was reported to have a range of actions beyond stimulation of erythropoiesis including vasoconstriction-dependent hypertension, stimulating angiogenesis, and promoting cell survival via activation of EPO receptors resulting in anti-apoptotic effects on ischemic tissues. (wikipedia.org)
  • The clinical approval of recombinant human erythropoietin in 1989 dramatically changed the treatment of anemia of chronic kidney disease, but randomized controlled trials yielded disappointing results when erythropoiesis-stimulating agents (ESAs) were used to raise hemoglobin to normal levels. (ccjm.org)
  • However, the process is multifactorial, with several other contributing factors: absolute and functional iron deficiency, folate and vitamin B 12 deficiencies, reduced red blood cell life span, and suppression of erythropoiesis by the uremic milieu. (ccjm.org)
  • The excess free α chains aggregate and precipitate in erythroblasts, leading to damage of cell membranes and reactive oxygen species (ROS) generation, leading to ineffective erythropoiesis. (bloodjournal.org)
  • Ineffective erythropoiesis is characterized by an expansion of immature erythroblasts associated with apoptosis of mature erythroblasts at the polychromatophilic stage, leading to a major reduction of red cell production. (bloodjournal.org)
  • ROS may also stimulate growth differentiation factor 11 (GDF11) expression, a novel actor in ineffective erythropoiesis that causes erythroid expansion of immature erythroblasts and inhibition of end-stage erythroid maturation. (bloodjournal.org)
  • Proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1, and interleukin-6 have been shown to disrupt multiple aspects of erythropoiesis, including reduction of renal erythropoietin secretion, suppression of erythropoietin activity in red blood cell precursors in the bone marrow level, and reduction of bioavailability of iron stores for hemoglobin synthesis. (ahajournals.org)
  • Erythropoietin , or its alternative erythropoetin or EPO , is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. (codagu.com)
  • Hemoglobin variability (Hb-var) in patients with chronic kidney disease has been stipulated to be a result of exogenous treatment with erythropoiesis stimulating agents (ESA) and has been related to mortality in dialysis patients. (jove.com)
  • Bone marrow aspiration usually reveals an erythroid hyperplasia, with increased marrow iron (dogs) and a concurrent mild reactive lymphocytosis and plasmacytosis, compatible with an ineffective erythropoiesis. (eclinpath.com)
  • Hematopoietic stem cells but not multipotent progenitors drive erythropoiesis during chronic erythroid stress in EPO transgenic mice. (uzh.ch)
  • Concurrently, Cdc42 deficiency caused anemia and splenomegaly accompanied with decreased bone marrow erythroid burst-forming units (BFU-Es) and colony-forming units-erythroid (CFU-Es) activities and reduced immature erythroid progenitors, suggesting that Cdc42 deficiency causes a block in the early stage of erythropoiesis. (bloodjournal.org)
  • The increased myelopoiesis and decreased erythropoiesis of the knockout mice are associated with an altered gene transcription program in hematopoietic progenitors, including up-regulation of promyeloid genes such as PU.1, C/EBP1α, and Gfi-1 in the common myeloid progenitors and granulocyte-macrophage progenitors and down-regulation of proerythroid gene such as GATA-2 in the megakaryocyte-erythroid progenitors. (bloodjournal.org)
  • RBCs are produced by erythropoiesis, which is an erythropoietin (EPO)-dependant cell development process in which a nucleus-containing erythroid precursor is differentiated to become a hemoglobin-containing enucleated RBC [ 7 ]. (biomedcentral.com)
  • 1 It is a heterogeneous disorder in which several pathophysiologic mechanisms may result in blocked erythropoiesis at different stages along the erythroid differentiation pathway. (aappublications.org)
  • In order to study the role of the cytokine interleukin-3 ( IL-3 ) and its signaling pathways in erythropoiesis of beta-thalassemia /HbE erythroid progenitor cells , CD34 positive cells were isolated from peripheral blood of patients and healthy subjects . (bvsalud.org)
  • Erythropoiesis requires rapid and extensive hemoglobin production. (jci.org)
  • Together, these studies provide insight into how heme is regulated to allow effective erythropoiesis, show that erythropoiesis fails when heme is excessive, and emphasize the importance of evaluating Ter119 - erythroid cells when studying erythroid marrow failure in murine models. (jci.org)
  • therefore, heme production must precede and may exceed the levels of heme utilization in hemoglobin during early erythropoiesis. (jci.org)
  • Imbalance in the relative quantity of α-globin and β-globin chains results in early apoptosis of maturing nucleated erythroid cells with hematopoietic expansion in an attempt for potential compensation, a state often referred to as ineffective erythropoiesis leading to chronic hemolytic anemia without significant reticulocytosis and an array of secondary pathophysiologic mechanisms. (ashpublications.org)
  • Erythropoietin stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells (erythrocytes). (beringomega.org)
  • Hematopoietic stem cells (HSCs) and myeloid progenitors in MDS have not been extensively characterized. (stanford.edu)
  • It's been suggested that this anti-apoptotic activity of lincRNA-EPS on erythroid progenitors may be at least partly functionally linked to the inhibited manifestation from the pro-apoptotic gene through a still 151126-84-0 supplier not really defined system [29]. (cylch.org)
  • Btk is required for an efficient response to erythropoietin and for SCF-controlled protection against TRAIL in erythroid progenitors. (ox.ac.uk)
  • Regulation of survival, expansion, and differentiation of erythroid progenitors requires the well-controlled activity of signaling pathways induced by erythropoietin (Epo) and stem cell factor (SCF). (ox.ac.uk)
  • As a result, expansion of erythroid progenitors lacking Btk is impaired at limiting concentrations of Epo and SCF. (ox.ac.uk)
  • Erythropoietin has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in humans) by promoting their survival through protecting these cells from apoptosis, or cell death. (wikipedia.org)
  • IL-3, IL-6, glucocorticoids, and SCF) involved in the development of erythroid lineage from multipotent progenitors. (wikipedia.org)
  • Background Diamond-Blackfan anemia is a rare, pure red blood cell aplasia of childhood due to an intrinsic defect in erythropoietic progenitors. (haematologica.org)
  • The bone marrow is normocellular, but erythroid precursors are absent or their numbers markedly decreased, because their progenitors are unable to differentiate and are prone to apoptosis. (haematologica.org)
  • The process of hematopoietic differentiation involves the generation of multilineage progenitors that are restricted to either the myeloid or lymphoid lineages (the common myeloid progenitor [ 1 ] and the common lymphoid progenitor [ 2 ]), and further differentiation of these pluripotent cells generates mature erythroid, megakaryocytic, myeloid, or lymphoid cells ( 3 ). (rupress.org)
  • At present, the most well-established function of EpoR is to promote proliferation and rescue of erythroid (red blood cell) progenitors from apoptosis. (wikipedia.org)
  • Primary role of EpoR is to promote proliferation of erythroid progenitor cells and rescue erythroid progenitors from cell death. (wikipedia.org)
  • Based on current evidence, it is still unknown whether Epo/EpoR directly cause "proliferation and differentiation" of erythroid progenitors in vivo, although such direct effects have been described based on in vitro work. (wikipedia.org)
  • So far, there is no sufficient evidence that in vivo, EpoR signaling can induce erythroid progenitors to undergo cell division, or whether Epo levels can modulate the cell cycle. (wikipedia.org)
  • CFU-e progenitors enter the cell cycle at the time of GATA-1 induction and PU.1 suppression in a developmental manner rather than due to EpoR signaling. (wikipedia.org)
  • It is unknown whether EpoR signaling plays a permissive (i.e. induces only survival) or an instructive (i.e. upregulates erythroid markers to lock progenitors to a predetermined differentiation path) role in early, multipotent progenitors in order to produce sufficient erythroblast numbers. (wikipedia.org)
  • The stages of differentiation of the red line starts from multipotent stem cells (also called hemocytoblasts), goes through common multipotent myeloid progenitors, unipotent stem cells, proerythroblasts (also called pronormoblast), basophilic normoblasts (also called erythroblast-secretes erythroferrone that inhibits the hepcidin secretion), intermediate normoblast-polychromatophilic, orthochrome normoblast (the nucleus is expelled) and reticulocytes (normally accounts for 1% of blood cells and lasts for 1-2 days until maturation to erythrocytes). (spandidos-publications.com)
  • There may be a left-shifted maturation sequence in erythroid progenitors (more immature than mature forms) and erythrophagia (of precursors or mature erythrocytes). (eclinpath.com)
  • Cdc42 deletion affected the number of early myeloid progenitors while suppressing erythroid differentiation. (bloodjournal.org)
  • The production of mature blood cells requires the sequential proliferation and differentiation of HSCs through a successive series of increasingly lineage-restricted intermediate progenitors including the common lymphoid progenitors (CLPs), the common myeloid progenitors (CMPs), the granulocyte-macrophage progenitors (GMPs), and the megakaryocyte-erythroid progenitors (MEPs). (bloodjournal.org)
  • When EPO binds to its ligand (receptor) on red blood cell progenitors it initiates a cascade which is mediated through the JAK2 signal transducers which ultimately effects the gene expression. (mlseducate.com)
  • From the CFU-E/proerythroblast (CD71 + Ter119 - cells) stage onward, erythroid progenitors exhibited excess heme content, increased cytoplasmic ROS, and increased apoptosis. (jci.org)
  • Erythropoietin is an essential hormone for red blood cell production. (wikipedia.org)
  • Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation. (wikipedia.org)
  • The burst-forming unit-erythroid (BFU-E) cells start erythropoietin receptor expression and are sensitive to erythropoietin. (wikipedia.org)
  • Subsequent stage, the colony-forming unit-erythroid (CFU-E), expresses maximal erythropoietin receptor density and is completely dependent on erythropoietin for further differentiation. (wikipedia.org)
  • Precursors of red cells, the proerythroblasts and basophilic erythroblasts also express erythropoietin receptor and are therefore affected by it. (wikipedia.org)
  • EPO binds to the erythropoietin receptor on the red cell progenitor surface and activates a JAK2 signalling cascade. (wikipedia.org)
  • High level erythropoietin receptor expression is localized to erythroid progenitor cells. (wikipedia.org)
  • Erythropoietin is produced primarily in the deep cortex and outer medulla of the kidneys by a special population of peritubular interstitial cells. (ccjm.org)
  • 17 The parenchymal cells of the liver also produce erythropoietin, but much less. (ccjm.org)
  • For example, anemia associated with chronic kidney disease could be related to decreased erythropoietin production, iron deficiency, effect of uremia on red blood cell membranes, and/or chronic inflammation. (abdominalkey.com)
  • 2 ERFE is produced by erythroid precursors in the bone marrow on erythropoietin (EPO) stimulation and represses liver hepcidin production by a still unknown mechanism. (bloodjournal.org)
  • Erythropoietin, a 30.4-kDa glycoprotein growth factor produced primarily by kidney, is the key component of the homeostatic system for regulation of red blood cell mass and tissue oxygen delivery. (ahajournals.org)
  • 21-24 Erythropoietin prevents the programmed cell death of erythrocyte progenitor cells and thereby stimulates their proliferation, maturation, and terminal differentiation. (ahajournals.org)
  • 60 mL/min) is associated with diminished erythropoietin production and a progressive decrease in hemoglobin values that is linearly related to reduction in GFR. (ahajournals.org)
  • Eva Bonsdorff and Eeva Jalavisto continued to study red cell production and later called the hemopoietic substance erythropoietin. (codagu.com)
  • Their research demonstrated that the gene for erythropoietin encoded the production of EPO in mammalian cells that is biologically active in vitro and in vivo. (codagu.com)
  • Erythropoietin has its primary effect on red blood cells by promoting red blood cell survival through protecting these cells from apoptosis. (codagu.com)
  • Specifically, the colony forming unit-erythroid (CFU-E) is completely dependent on erythropoietin. (codagu.com)
  • MASL1 induces erythroid differentiation in human erythropoietin-dependent CD34+ cells through the Raf/MEK/ERK pathway. (nih.gov)
  • Preclinically, recombinant erythropoietin has been shown to increase tumor oxygenation, but the direct effects of recombinant erythropoietin on tumor cells that express erythropoietin receptor are not yet fully characterized. (aacrjournals.org)
  • This study examined the effects of exogenous recombinant erythropoietin on rodent mammary adenocarcinoma cells (R3230) in vitro and in vivo , and determined the effects of systemic recombinant erythropoietin on tumor growth delay in Taxol treatment. (aacrjournals.org)
  • We showed that systemic recombinant erythropoietin treatment of rats bearing R3230 mammary carcinomas induced an increase in phospho-Akt levels within tumor cells. (aacrjournals.org)
  • This was associated with a decrease in the frequency of apoptotic cells in tumors from recombinant erythropoietin-treated animals, but did not noticeably affect tumor growth rate. (aacrjournals.org)
  • Activation of erythropoietin-mediated signaling in R3230 cells was associated with dose-dependent inhibition of apoptosis in response to Taxol treatment and serum starvation, an effect that was blocked by the addition of a phosphatidylinositol-3-kinase inhibitor. (aacrjournals.org)
  • This study shows direct recombinant erythropoietin-mediated activation of specific intracellular signaling pathways in mammary adenocarcinoma cells in vivo and in vitro . (aacrjournals.org)
  • Modulation of tumor apoptosis pathways by recombinant erythropoietin may have negative consequences by decreasing the chemosensitivity and radiosensitivity of erythropoietin receptor-positive breast tumors, although it did not have any obvious effects on growth with or without chemotherapy in this model. (aacrjournals.org)
  • Erythropoietin is a glycoprotein hormone that regulates RBC production by binding to its specific cell surface receptor (EpoR) expressed in erythroid progenitor cells. (aacrjournals.org)
  • Since the discovery of EpoR expression in cancer cells, there have been in vitro reports linking erythropoietin-EpoR signaling to the modulation of tumor cell proliferation ( 2 , 7 ), chemosensitivity ( 8 ), and radiosensitivity ( 9 ). (aacrjournals.org)
  • Recent clinical trials have raised concerns regarding the value of recombinant erythropoietin treatment during chemoradiation therapy of cancer patients ( 11 , 12 ), although a recent metaanalysis showed that not only did recombinant erythropoietin treatment improve hemoglobin levels and decrease the need for transfusions in anemic cancer patients, but also provided suggestive but inconclusive evidence that recombinant erythropoietin may improve overall survival in these patients ( 13 ). (aacrjournals.org)
  • This study is the first to characterize the direct effects of recombinant erythropoietin on mammary adenocarcinoma cells both in vitro and in vivo , focusing on the ability of recombinant erythropoietin to modulate tumor growth, apoptosis, and the activation of the PI3K/Akt and p44/42 MAPK pathways ( 14 , 15 ). (aacrjournals.org)
  • In a healthy condition, renal secretion of erythropoietin (EPO) plays a crucial role in red blood cell (RBC) proliferation and differentiation, and insufficient EPO production in ESRD patients leads to both decreasing RBC production and a 30% ~ 70% shorter RBC lifespan [ 5 ]. (biomedcentral.com)
  • FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. (childrenshospital.org)
  • At concentrations found in the circulation of malaria-infected patients, MIF suppressed erythropoietin-dependent erythroid colony formation. (rupress.org)
  • Collectively, these observations have served to focus attention on the pathogenesis of the bone marrow suppression that occurs during malaria infection and on the mechanisms that may contribute to the resistance of erythroid progenitor cells to the action of circulating erythropoietin ( 21 ). (rupress.org)
  • In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. (plos.org)
  • Here, we critically review the state of art about mesenchymal stem cell role in myelodysplastic syndromes and acute myeloid leukemia, focusing on immune escaping mechanisms as a target for available and future anticancer therapies. (hindawi.com)
  • Recent evidences support the notion that patients with myeloid malignancies may present bone marrow microenvironment alterations in terms of abnormal hematopoietic-to-stromal cell interactions, relative deficiency of hematopoietic growth factors, and aberrant release of inhibitors [ 1 ]. (hindawi.com)
  • MDS are clonal disorders of myeloid stem cells. (medscape.com)
  • These syndromes are characterized by ineffective hematopoiesis manifested in morphologic dysplasia of hematopoietic precursors, one or more peripheral blood cytopenias, and a propensity to progress to acute myeloid leukemia (AML). (medscape.com)
  • [ 3 , 4 ] as a type of MDS with one or more cytopenias and dysplastic changes in two or more of the myeloid lineages (erythroid, granulocytic, or megakaryocytic). (medscape.com)
  • It is thought that erythroid differentiation is primarily dependent on the presence and induction of erythroid transcriptional factors such as GATA-1, FOG-1 and EKLF, as well as the suppression of myeloid/lymphoid transcriptional factors such as PU.1. (wikipedia.org)
  • We report here that inducible deletion of cdc42 in cdc42 -floxed mouse bone marrow by the interferon-responsive, Mx1-Cre -mediated excision led to myeloid and erythroid developmental defects. (bloodjournal.org)
  • Cdc42-deficient mice developed a fatal myeloproliferative disorder manifested by significant leukocytosis with neutrophilia, myeloid hyperproliferation, and myeloid cell infiltration into distal organs. (bloodjournal.org)
  • 6 - 9 Ectopic expression or gene knockout studies of specific transcription factors have provided convincing evidence that blood cell lineage fate, such as myeloid, erythroid, or lymphoid commitment, can be switched by altered expression patterns of transcription factors including PU.1, C/EBPα, Gfi-1, and/or GATA2. (bloodjournal.org)
  • Her bone tissue marrow uncovered 20-30% cellularity with minor erythroid hyperplasia and minor myeloid and megakaryocyte hypoplasia. (calcipotriol.net)
  • Myeloid precursors are normal, as are megakaryocytes. (renalandurologynews.com)
  • The mean values of the hemoglobin, the reticulocyte count, and the myeloid/erythroid ratio at the onset of the disease were 4.75 ± 1.79 g/dL, 0.14 ± 0.16, and 39.4 ± 27.08, respectively. (aappublications.org)
  • Bone marrow aspirate and biopsy were assessed for cellularity, state of various lineages, and erythroid/myeloid ratios. (aappublications.org)
  • Acute myeloid (myelogenous, myelocytic, myeloblastic) leukemia (AML) consists of a group of malignant disorders characterized by the replacement of normal bone marrow with abnormal, primitive hematopoietic cells. (medscape.com)
  • Consistent with this observation, ETV7 expression enhanced the colony-forming and self-renewal activities of primary myeloid Pten − / − cells. (springer.com)
  • Based on flow cytometric analysis with antibodies specific for lymphoid, myeloid, and erythroid cell types, the cellularity and distribution of hematopoietic cells in ETV7Tg BM, spleen, and thymus are similar to those in WT mice. (springer.com)
  • Nonetheless, ETV7Tg BM cells proliferated faster in long-term culture, in which ETV7 enhanced proliferation of myeloid cells compared with that of control WT myeloid cells. (springer.com)
  • report that ribosomal deficiencies in individuals with either DBA or Del(5q) MDS lead to insufficient globin protein synthesis but normal heme synthesis, which results in excess heme and reactive oxygen species in early erythroid precursors and proerythroblast cell death. (sciencemag.org)
  • Treating affected cells with an inhibitor of heme synthesis improves erythroid cell output in cell culture. (sciencemag.org)
  • The cells that can more rapidly and effectively export heme or can slow heme synthesis preferentially survive and appropriately mature. (sciencemag.org)
  • Our data further suggest that therapies that decrease heme synthesis (or facilitate heme export) could improve the red blood cell production of persons with DBA, del(5q) MDS, and perhaps other macrocytic anemias. (sciencemag.org)
  • If all four globin loci deletions occur, there can be no synthesis of any normal hemoglobin (HbA, HbA2, HbF). (clinicaladvisor.com)
  • However, excess free heme is toxic, leading to cell apoptosis, so that a tight balance between heme synthesis and heme use is required. (uw.edu)
  • Tfr1 is highly expressed on differentiating erythrocytes, reflecting their substantial iron requirement to support hemoglobin synthesis ( Ponka and Lok, 1999 ). (biologists.org)
  • Whereas the red cell lacks de novo lipid synthesis, the phospholipids in the plasma membrane are continuously renewed by a deacylation/reacylation mechanism (the Lands Pathway). (chori.org)
  • 3 Depending on the specific α/β-globin ratio and capacity for fetal hemoglobin synthesis, patients can present at various ends of the phenotype spectrum of biological and clinical severity. (bloodjournal.org)
  • He showed a structure containing a macrophage surrounded by developing erythroblasts ( Bessis, 1958 ) and concluded that macrophages actively participate in erythroid development by providing iron for heme synthesis and by phagocytosing expelled nuclei during final erythroid differentiation ( Bessis and Breton-Gorius, 1962 ). (frontiersin.org)
  • Thalassemia are a group of inherited blood disorders caused by the decrease or absence of beta-globin chain synthesis will be determined with decrease in erythrocyte hemoglobin, decreased production of erythrocytes and anemia. (ijbmph.com)
  • The reticulocyte is still capable of hemoglobin synthesis, although it is anucleated. (spandidos-publications.com)
  • Treatment of Thalassemia/Thalassemia is an autosomal recessive hereditary chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains (α-thal) or β-globin chains (β-thal) which compose the major adult hemoglobin (HbA), a tetramer of α 2 β 2 . (rxharun.com)
  • What this means is that EPO stimulates synthesis of red cell RNA, such as the production of hemoglobin. (mlseducate.com)
  • We propose that an equilibrium state exists between Gadd34/PP1c and the opposing heme-regulated inhibitor kinase during hemoglobin synthesis in the reticulocyte. (asm.org)
  • Reducing heme synthesis in FLVCR1-defient animals via genetic and biochemical approaches improved the anemia, implying that heme excess causes, and is not just associated with, the erythroid marrow failure. (jci.org)
  • Mutations in the haemoglobin genes cause disorders that are qualitative anomalousities in the synthesis of haemoglobin (e.g., reap hook cell disease) and some that are quantitative abnormalities that pertain to the rate of haemoglobin synthesis (e.g., the thalassemias) (Weatherall. (blogspot.com)
  • Cooleys anaemia is yet a nonher disorder caused by a defect in haemoglobin synthesis.Autoimmune hemolytic anaemia is a syndrome in which individuals produce antibodies directed against one of their own erythrocyte tissue layer antigens. (blogspot.com)
  • Therefore, cells must balance heme synthesis with its use. (sciencemag.org)
  • Molecular defects in the α-globin gene cluster on chromosome 16 or the β - globin gene cluster on chromosome 11 result in defective hemoglobin synthesis. (ashpublications.org)
  • This results in insufficient globin protein, excess heme and excess reactive oxygen species in early erythroid precursors, and CFU-E (colony-forming unit-erythroid)/proerythroblast cell death. (sciencemag.org)
  • The CFU-Es (Colony-forming unit-erythroid) are red blood cell progenitor cells that develop from BFU-Es (Burst-forming unit-erythroid). (mlseducate.com)
  • Inducibly proliferating erythroid (IPE) cells were isolated with surface receptors similar to colony forming unit-erythroid (CFU-Es), and after removal of ectopic c-Myc expression cells hemoglobinized, decreased in cell size to that of native RBCs, and enucleated achieving cultures with 17% enucleated cells. (biomedcentral.com)
  • Cats viremic with FeLV-C develop pure red cell aplasia (PRCA), characterized by a block in erythroid differentiation at the CFU-E (colony-forming unit-erythroid)-proerythroblast stage, reticulocytopenia, and severe anemia ( 4 , 5 ). (sciencemag.org)
  • Editing at this site met our preclinical goals including robust, long-term induction of fetal hemoglobin and maintenance of normal hematopoietic stem/progenitor cell function," said Charles Albright, Ph.D., Chief Scientific Officer, Editas Medicine. (ptcommunity.com)
  • EPO production, or the administration of EPO as a drug, early progenitor cell numbers are amplified and, in turn, give rise to increased numbers of erythrocytes. (mhmedical.com)
  • Genetic engineering of adult erythroid progenitor cells with an inducible c-Myc vector established an erythroid progenitor cell line that could produce RBCs, demonstrating the potential of this approach to produce large quantities of RBCs and modified RBC products. (biomedcentral.com)
  • Role of interleukin-3 and signaling pathways on beta-thalassemia/HbE erythroid progenitor cell in culture. (bvsalud.org)
  • After 7 days of culture the highest percent erythroid progenitor cell viability was obtained with cells from healthy subjects , while the lowest percentage was found in those from splenectomized beta-thalassemia /HbE. (bvsalud.org)
  • When the erythroid progenitor cell lines are infected, apoptosis ensues, causing an abrupt cessation of all red blood cell production. (clinicaladvisor.com)
  • Dr. Abkowitz identified, through expression cloning, a membrane transport protein (FLVCR) that is critical for the survival of early erythroid precursors (CFU-E/proerythroblasts) and demonstrated that it exports cytoplasmic heme. (uw.edu)
  • Analysis of bone marrow collected eight to 16 weeks post-infusion demonstrated that robust fetal hemoglobin induction was achieved when targeting HBG1/2 promoters. (ptcommunity.com)
  • Notably, editing HBG1/2 promoters upregulated fetal hemoglobin with superior repopulation of red blood cell precursors as compared to editing the BCL11A e site. (ptcommunity.com)
  • Increased production of fetal hemoglobin can be beneficial to patients with sickle cell disease or beta-thalassemia. (ptcommunity.com)
  • Due to the complete absence of alpha chains, the predominant fetal hemoglobin is a tetramer of gamma-chains (Bart hemoglobin) that has essentially no oxygen carrying capacity. (proteopedia.org)
  • Fetal hemoglobin (HbF) consists of two α-globin chains and two γ-globin chains (α 2 γ 2 ), which is present in high levels in fetal and newborn human blood. (intechopen.com)
  • Treatment including Change of expression and production of HbF, Hematopoietic stem cell transplantation and Maintenance Treatment such as chelators therapy, Induction of fetal hemoglobin production by using Hydroxia urea, use of immunomodulator agents and Molecular Therapy by targeting of genes involving in HbF expression.in this article we review the thalassemia disorder and discuss on molecular basis, clinical features and treatment. (ijbmph.com)
  • Fetal hemoglobin (HbF) can be increased. (renalandurologynews.com)
  • THALAMOSS is aimed at development of universal sets of markers and techniques for stratification of β-thalassaemia patients into treatment subgroups for (a) onset and frequency of blood transfusions, (b) choice of iron chelation, (c) induction of fetal hemoglobin, (d) prospective efficacy of gene-therapy. (europa.eu)
  • CAMBRIDGE, Mass., Dec. 02, 2018 (GLOBE NEWSWIRE) -- Editas Medicine, Inc. (NASDAQ: EDIT), a leading genome editing company, today announced results from experiments to demonstrate expanded CRISPR genome editing strategies in hematopoietic stem cells for the treatment of sickle cell disease and beta-thalassemia. (ptcommunity.com)
  • Editing at the HBG1/2 site is a differentiated approach for development of a human therapeutic for the treatment of sickle cell disease and beta-thalassemia as compared to other medicines currently under development that edit at the BCL11Ae site. (ptcommunity.com)
  • These findings further support our novel approach to developing a medicine for the potential treatment of sickle cell disease and beta-thalassemia. (ptcommunity.com)
  • also known as sickle cell disease. (proteopedia.org)
  • HbA2 : biology, clinical relevance and a possible target for ameliorating sickle cell disease. (nih.gov)
  • Emerging Genetic Therapy for Sickle Cell Disease. (childrenshospital.org)
  • Parvovirus B19 (fifth disease) can also cause red cell aplasia, but a significant anemia is only seen in children with an underlying hemolytic anemia and shortened red cell survival, such as hereditary spherocytosis or sickle-cell disease. (renalandurologynews.com)
  • However, patients with decreased erythrocytes or erythrocyte life-spans (human immunodeficiency virus [HIV], sickle cell disease, spherocytosis, or thalassemia) are predisposed to transient aplastic crisis, possibly requiring red blood cell transfusions. (clinicaladvisor.com)
  • The loss of three alpha genes results in high levels of a tetramer of four beta chains (hemoglobin H), causing a severe and life-threatening anemia known as hemoglobin H disease. (proteopedia.org)
  • Affected individuals have small red cells and a mild anemia (microcytosis). (proteopedia.org)
  • We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that Gpx4 is essential for preventing receptor-interacting protein 3 (RIP3)-dependent necroptosis in erythroid precursor cells. (nih.gov)
  • Although genetic ablation of Rip3 normalizes reticulocyte maturation and prevents anemia, ROS accumulation and lipid peroxidation in Gpx4-deficient cells remain high. (nih.gov)
  • Mutant beta globin causes sickle cell anemia. (genecards.org)
  • Diseases associated with HBB include Beta-Thalassemia and Sickle Cell Anemia . (genecards.org)
  • How this causes erythroid marrow failure, and specifically macrocytic anemia, remains uncertain. (sciencemag.org)
  • Anemia is moderate (mean Hb of 8.5 g/dL), with low MCV (mean MCV 54.0 fL), low MCH (mean 16.6 pg), and hemoglobin electrophoresis can show between 5 and 30% HbH. (clinicaladvisor.com)
  • As it precipitates in circulating red blood cells (RBCs), hemolytic anemia develops. (clinicaladvisor.com)
  • The zebrafish chianti ( cia ) mutant manifests a hypochromic, microcytic anemia after the onset of embryonic circulation, indicative of a perturbation in red blood cell hemoglobin production. (biologists.org)
  • The physiologic basis of red cell production and destruction provides an understanding of the mechanisms that can lead to anemia. (mhmedical.com)
  • Anemia is defined as a hemoglobin concentration less than 13.0 g/dL for men and less than 12.0 g/dL for premenopausal women. (ccjm.org)
  • The causes of anemia in children can be classified by the physiological process of red blood cell (RBC) production and loss or by morphology based on the size of the RBCs. (abdominalkey.com)
  • Likewise, a microcytic, hypochromic (decrease in mean corpuscular hemoglobin) anemia can occur due to the coexistence of iron deficiency and lead poisoning. (abdominalkey.com)
  • 12.0 g/dL in women) takes into account known gender differences in distribution of hemoglobin values, 16 whereas the National Kidney Foundation defines anemia as hemoglobin ≤12 g/dL in men and postmenopausal women. (ahajournals.org)
  • Published reports in CHF populations have used these and other study-specific definitions of anemia (including other arbitrary or statistically defined hemoglobin and hematocrit categories and administrative diagnostic codes from hospital records). (ahajournals.org)
  • Hemolytic anemia is a form of anemia due to hemolysis , the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, but usually in the spleen ). (wikipedia.org)
  • Symptoms of hemolytic anemia are similar to other forms of anemia ( fatigue and shortness of breath ), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension . (wikipedia.org)
  • Runners can suffer hemolytic anemia due to " footstrike hemolysis ", owing to the destruction of red blood cells in feet at foot impact. (wikipedia.org)
  • These aggregates cause the death of red blood cells and their precursors, causing very severe anemia. (rxharun.com)
  • Infection of MIF knockout mice with Plasmodium chabaudi resulted in less severe anemia, improved erythroid progenitor development, and increased survival compared with wild-type controls. (rupress.org)
  • The anemia of malaria infection is the result of pathologic processes that act both to accelerate red cell destruction and to inhibit new red cell production ( 3 - 5 ). (rupress.org)
  • Importantly, recent studies have led to the conclusion that enhanced red cell clearance alone does not adequately explain the development of malarial anemia, especially in those patients who develop a severe, life-threatening disease ( 8 , 9 ). (rupress.org)
  • Diamond-Blackfan anemia (DBA) is a severe red cell (erythroid) aplasia that usually presents soon after birth. (renalandurologynews.com)
  • Importantly, DBA usually presents as a pure red cell aplasia with a severe often macrocytic anemia, but normal platelet and leukocyte counts. (renalandurologynews.com)
  • Severe anemia is a frequent presenting feature, and cautious transfusion of packed red blood cells is often the most urgent first line treatment and used to maintain the hemoglobin during the first year of life. (renalandurologynews.com)
  • Diamond-Blackfan anemia (DBA) is characterized by decreased or absent bone marrow erythroid precursor cells, severe anemia, and reticulocytopenia, and it is frequently associated with a variety of somatic malformations. (aappublications.org)
  • Anemia is usually normocytic, with a lower-than-expected reticulocyte count for the hemoglobin level. (medscape.com)
  • Parvovirus B19 causes erythema infectiosum (fifth or "slapped check" disease in children), transient aplastic crisis in patients with diseases reducing the life-span of a normal red blood cells, persistent anemia in immunocompromised patients, and a symmetric polyarthritis in adults that can be acute or chronic. (clinicaladvisor.com)
  • Transient aplastic crisis in patients with sickle cell and other hemolytic disorders may present with symptoms of profound anemia (dyspnea, high cardiac output heart failure, stroke, or even death). (clinicaladvisor.com)
  • 2008). The principal(prenominal) causes of genus Anemia are blood overtaking, labor of too few red blood cells by the atomic progeny 76 marrow or a rapid desolation of cells.Haemoglobin, a protein, present in the red blood cells is involved in the transport of oxygen from the lungs to all in all the other organs and tissues of the body. (blogspot.com)
  • The mutation ca employ reap hook cell anemia is a single nucleotide substitution (A to T) in the codon for amino acid 6. (blogspot.com)
  • The form of haemoglobin in persons with reap hook cell anemia is referred to as HbS. (blogspot.com)
  • Alas2 -/- mutation results in murine embryonic lethality, as it causes severe anemia resulting from arrested erythroid differentiation at the proerythroblast stage due to heme insufficiency 10 . (nature.com)
  • Mice with FLVCR that is deleted neonatally develop a severe macrocytic anemia with proerythroblast maturation arrest, which suggests that erythroid precursors export excess heme to ensure survival. (sciencemag.org)
  • Activins are involved in differentiation of erythroid precursors and erythroleukemia cell lines, neuronal survival, stimulation of insulin and anterior pituitary hormone secretion, regulation of the menstrual cycle, increasing FSH production and granulosa cell differentiation by binding to follistatin, an FSH release inhibitor. (thefreedictionary.com)
  • In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. (frontiersin.org)
  • The first, and rate-limiting, enzymatic step is mediated by 5-aminolevulinate synthase 2 (ALAS2) in erythroblasts and ALAS1 in all other cells. (jci.org)
  • This differential regulation likely reflects the fact that 95% of rbc protein content is hemoglobin, and thus developing erythroblasts need to produce high levels of heme. (jci.org)
  • An adult human body contains 3-5 g of iron, much of which is supplied to developing erythroblasts for incorporation within the haem group of haemoglobin (70% of bodily iron) [ 3 ]. (mdpi.com)
  • To study the changes in hemoglobin concentrations during the first week of sepsis in the setting of Internal Medicine (IM) units, and their correlation to survival. (biomedcentral.com)
  • Data on blood transfusions was also collected, we examined the correlation between hemoglobin concentrations during the first week of sepsis and survival, the effect of blood transfusion was also assessed. (biomedcentral.com)
  • While hemoglobin level on admission exhibit independent correlation with survival, blood transfusion do not. (biomedcentral.com)
  • In the present study, we characterized acute changes in hemoglobin levels during the first week of sepsis in patients admitted to IM (Internal Medicine) departments and its correlation to in-hospital mortality and overall survival. (biomedcentral.com)
  • Maintaining cellular redox balance is vital for cell survival and tissue homoeostasis because imbalanced production of reactive oxygen species (ROS) may lead to oxidative stress and cell death. (nih.gov)
  • This results in differentiation, survival and proliferation of the erythroid cell. (wikipedia.org)
  • Patients with the most severe forms (β-thalassemia major) require chronic red blood cell transfusion for survival and iron chelation to prevent increased plasma iron and formation of non-transferrin-bound iron (NTBI) with its related organ damage (eg, liver, heart, and/or endocrine organs). (bloodjournal.org)
  • Activation of the transcription factor signal transducer and activator of transcription (STAT)5 is involved in various aspects of hematopoiesis, affecting cell proliferation, differentiation, and cell survival. (rupress.org)
  • Subsequent differentiation stages (proerythroblast to orthochromatic erythroblast) involve a decrease in cell size and eventual expulsion of the nucleus, and are likely dependent upon EpoR signaling only for their survival. (wikipedia.org)
  • Together, these data suggest that EpoR in erythroid differentiation may function primarily as a survival factor, while its effect on the cell cycle (for example, rate of division and corresponding changes in the levels of cyclins and Cdk inhibitors) in vivo awaits further work. (wikipedia.org)
  • UNC2025 inhibited MERTK in bone marrow leukemia cells and had significant therapeutic effects in xenograft models, with dose-dependent decreases in tumor burden and consistent two-fold increases in median survival, irrespective of starting disease burden. (aacrjournals.org)
  • Although all bone marrow cells are infected ( 8 ), white cell and platelet production remain normal, which suggests that FLVCR is uniquely important for CFU-E-proerythroblast survival or differentiation. (sciencemag.org)
  • The main component of RBC is hemoglobin (Hb) which consists of four subunits of globin chain with heme group at the center of each subunit. (intechopen.com)
  • We cultured marrow cells from DBA ( n = 3) and del(5q) MDS ( n = 6) patients and determined how heme (a toxic chemical) and globin (a protein) are coordinated. (sciencemag.org)
  • Heme is synthesized by all aerobic cells and is a critical component of cytochromes, catalases, glutathione peroxidase, hydroxylases, and nitric oxide synthase, as well as myoglobin and hemoglobin. (uw.edu)
  • It also appears that FLVCR is important in placenta, liver, duodenum, brain and macrophage, and may serve to protect these non-erythroid tissues from high intercellular heme flux and/or facilitate heme trafficking and systemic iron hemostasis. (uw.edu)
  • Iron is a crucial metal for normal development, being required for the production of heme, which is incorporated into cytochromes and hemoglobin. (biologists.org)
  • In erythroid cells, most iron is carried to the mitochondria, where it is incorporated with protoporphyrin to produce heme. (biologists.org)
  • Hemoglobin is a globular protein consisting of 4 polypeptide chains, each having an heme group and an iron atom in the center of the heme group. (uvigo.es)
  • Expression of the cell surface FLVCR1 isoform, but not the mitochondrial FLVCR1 isoform, restored normal rbc production, demonstrating that cellular heme export is essential. (jci.org)
  • In addition to serving as a prosthetic group for enzymes and a hemoglobin structural component, heme is a crucial homeostatic regulator of erythroid cell development and function. (nature.com)
  • In this study, we elucidated a lncRNA (UCA1)-mediated mechanism that regulates heme metabolism in human erythroid cells. (nature.com)
  • UCA1 depletion predominantly impairs heme biosynthesis and arrests erythroid differentiation at the proerythroblast stage. (nature.com)
  • In addition, heme is a vital structural component of hemoglobin. (nature.com)
  • We further demonstrate that FLVCR mediates heme export from macrophages that ingest senescent red cells and regulates hepatic iron. (sciencemag.org)
  • Aerobic cells require heme, a cyclic tetrapyrole containing a centrally chelated iron. (sciencemag.org)
  • Heme also initiates globin transcription through inhibiting the DNA binding of the repressor, Bach1 ( 1 ), and globin translation through inhibiting substrate phosphorylation by the repressor, erythroid-specific eukaryotic initiation factor 2α kinase ( 2 ). (sciencemag.org)
  • Biochemical analysis of the hemoglobin-producing reticulocyte (an erythrocyte precursor) revealed that the decreased hemoglobin content in the Gadd34 -null erythrocyte is due to the reduced initiation of the globin translation machinery. (asm.org)
  • J) Quantification of splenic BrdU + /TER119 + cells determined by flow cytometry. (nih.gov)
  • After culturing the cells in the presence or absence of IL-3 , cell viability was measured by trypan blue staining and apoptotic cells were analyzed by flow cytometry . (bvsalud.org)
  • Flow Cytometry test size is recommended as 20 ul reagent / 100 ul of whole blood or 10^6 cells in a suspension. (novusbio.com)
  • JAK2 V617F has oncogenic properties and is responsible for uncontrolled cell proliferation, inhibition of apoptosis, genetic instability via induction of proto‐oncogenes, reactive oxygen species and promotion of mitotic recombination. (els.net)
  • LNCRNAS IN Regular HEMATOPOIESIS Many lineage-specific lncRNAs have already been already recognized in the introduction of bloodstream cells, although many of them have not however been functionally characterized. (cylch.org)
  • She is applying this approach to understand the mechanisms by which human HSCs reconstitute hematopoiesis after transplantation, the pathophysiology of clinical marrow failure syndromes, and the kinetics of cancer stem cell expansion. (uw.edu)
  • Address correspondence to Malcolm A.S. Moore, Laboratory of Developmental Hematopoiesis, Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. (rupress.org)
  • Hematopoiesis is initiated by a relatively small number of multipotent self-renewing hematopoietic stem cells (HSCs) that generate large numbers of differentiated progeny by a process of amplification and progressive lineage restriction. (rupress.org)
  • Hematopoiesis is a highly orchestrated process involving multilineage blood cell development. (bloodjournal.org)
  • We find that inhibition of let-7 in the adult hematopoietic system recapitulates fetal erythroid-dominant hematopoiesis. (rupress.org)
  • Hematopoiesis is a tightly controlled process in which stem and progenitor cells generate mature progeny to maintain a dynamic complement of blood cells that together support the physiological needs of oxygen transport, immune competence, and hemostasis. (rupress.org)
  • Direct and significant effects of EpoR signaling specifically upon the induction of erythroid-specific genes such as beta-globin, have been mainly elusive. (wikipedia.org)
  • Induction of proliferation by the EpoR is likely cell type-dependent. (wikipedia.org)
  • The potential mechanisms include the direct inhibition to the growth of erythroid precursor, induction of apoptosis, and disrupting iron metabolism. (biomedcentral.com)
  • Ezatiostat is an investigational agent in development for the treatment of a variety of neoplastic and non-neoplastic hematologic disorders, including myelodysplastic syndrome (MDS), and has demonstrated significant improvement in the induction of growth and differentiation of hematologic precursor stem cells as well as an increase in apoptosis of malignant cells. (biomedcentral.com)
  • In vitro induction of undifferentiated hESC to functionally mature blood cells may mimic the early hematopoietic development during human embryonic and fetal stages. (intechopen.com)
  • EPO inhibits apoptosis by removing the induction signal. (mlseducate.com)
  • If there is a deficiency of red blood cell mass, those cells undergo maturation to be released, while simultaneously the apoptosis induction signal is inhibited. (mlseducate.com)
  • We explored a new method to produce RBCs by inducibly expressing c-Myc in primary erythroid progenitor cells and evaluated the proliferative and maturation potential of these modified cells. (biomedcentral.com)
  • Primary erythroid progenitor cells were genetically modified with an inducible gene transfer vector expressing a single transcription factor, c-Myc, and all the gene elements required to achieve dox-inducible expression. (biomedcentral.com)
  • Induced proliferation of erythroid progenitor cells is a promising strategy for producing RBCs that has been explored with some success. (biomedcentral.com)
  • In the severe forms of beta-thalassemia, the excess alpha globin chains accumulate in the developing erythroid precursors in the marrow. (proteopedia.org)
  • For instances, hemoglobin A (HbA) consists of two α-globin chains and two β-globin chains (α 2 β 2 ), which is found in high levels of normal human blood. (intechopen.com)
  • Hemoglobin A 2 (HbA 2 ) consists of two α-globin chains and two δ-globin chains (α 2 δ 2 ), which is found in low levels of normal human blood and may be increased in the blood of patients with β-thalassemia. (intechopen.com)
  • Normal adult hemoglobin (hemoglobin A) is made of a pair of alpha globin chains and a pair of beta globin chains. (clinicaladvisor.com)
  • A reduction in the production of normal alpha globin chains results in a compensatory increase in beta chains, which alters the physiology of the red blood cell and results in the characteristic clinical and/or laboratory findings of the four types of alpha thalassemia. (clinicaladvisor.com)
  • Patients with alpha thalassemia-1 trait (alpha thalassemia minor) have two of the four globin loci deleted, and will have a mildly reduced MCV as well as MCHC with occasional target cells on a peripheral smear. (clinicaladvisor.com)
  • The most common non-deletional HbH disease is Hemoglobin H Constant Spring (HCS), resulting from the deletion of 2 alpha-globin genes and the Constant Spring mutation. (clinicaladvisor.com)
  • β-Thalassemias are monogenic diseases characterized by the lack or reduction of the hemoglobin β-globin chain expression resulting in an increase of the α/β globin ratio. (bloodjournal.org)
  • Recently, the small protein α hemoglobin-stabilizing protein (AHSP) was identified and found to specifically bind α-globin, stabilize its structure, and limit the toxic effects of excess α-globin, which are manifest in the inherited blood disorder β thalassemia. (jci.org)
  • In this issue of the JCI, Yu, Weiss, and colleagues show that AHSP is also critical to the formation and stabilization of normal amounts of hemoglobin, even when α-globin is deficient, indicating unique and previously unidentified roles for this molecule (see the related article beginning on page 1856). (jci.org)
  • HbVar: a relational database of human hemoglobin variants and thalassemia mutations at the globin gene server. (ijbmph.com)
  • Thalassemia is a relatively common single-gene disorder, with roughly 90% of patients having defective hemoglobin associated with mutations in the globin genes ( 8 ). (asm.org)
  • LncRNAs involved with erythroid differentiation The initial lncRNA to become related to reddish colored bloodstream cells was the murine Erythroid ProSurvival lincRNA (lincRNA-EPS), determined by RNA-sequencing as extremely specific among around 400 lncRNAs with modulated appearance during reddish colored bloodstream cells differentiation [29]. (cylch.org)
  • In this report, by using multiple knockout mouse models, we demonstrate that UFBP1 is essential for murine development and blood cell development. (prolekare.cz)
  • We found that Shp2 mutants associated with sporadic leukemias transform murine bone marrow cells, whereas NS mutants are less potent in this assay. (jove.com)
  • The rarity of inherited cytopenias, the paucity of affected primary human hematopoietic cells, and the sometime inadequacy of murine or induced pluripotential stem cell models mean it is difficult to acquire a greater understanding of them. (haematologica.org)
  • Having been focusing on basic and clinical research on hESC/hiPSC-derived functionally mature blood cells for long, our group has established an efficient method to induce large-scale production of multipotential hematopoietic progenitor cells by coculturing hESC/hiPSCs with murine hematopoietic niche-derived stromal cells [ 3 - 6 ]. (intechopen.com)
  • Co-cultivation with HZ or treatment with low-micromolar HNE inhibited growth of erythroid cells interfering with cell cycle without apoptosis. (biomedcentral.com)
  • We studied 46 consecutive patients with AL who underwent quantification of serum M-protein and clonal bone marrow plasma cells, as well as a comprehensive evaluation for end organ damage by MM. Using standard morphology and CD138 immunohistochemical staining, 57% and 80% of patients were found to have concomitant MM, respectively. (stanford.edu)
  • HBB (Hemoglobin Subunit Beta) is a Protein Coding gene. (genecards.org)
  • HZ and HZ-laden human monocytes inhibited growth of co-cultivated human erythroid cells and produced HNE that diffused to adjacent cells generating HNE-protein adducts. (biomedcentral.com)
  • As a second major effect, HZ and HNE inhibited protein expression of crucial receptors (R): transferrin R1, stem cell factorR, interleukin-3R and erythropoietinR. (biomedcentral.com)
  • Iron is subsequently delivered to the cell cytoplasm through the action of the transmembrane protein divalent metal transporter 1 (DMT1), which transports iron out of the endosome by means of a proton-coupled process. (biologists.org)
  • EpoR is a 52kDa peptide with a single carbohydrate chain resulting in an approximately 56-57 kDa protein found on the surface of EPO responding cells. (wikipedia.org)
  • In hematopoietic cells, EpoR signaling is known to activate several intracellular kinase pathways, including the Jak/Stat, phosphatidylinositol-3-kinase (PI3K)/Akt, and p44/42 mitogen-activated protein kinase (MAPK) pathways ( 6 ). (aacrjournals.org)
  • Haemoglobin is a molecule made up of iron and protein, which carries oxygen in the red blood cells in the blood around the body from the lungs to the tissues (e.g. muscles or brain) where this oxygen is essential to the functioning of the tissues. (enetmd.com)
  • When EPO binds to its ligand on the red blood cell activates the JAK2-STAT pathway, which ends in and up-regulation of transcription for BCL-2, which is an anti-apoptotic protein. (mlseducate.com)
  • This anti-apoptotic protein rests on the cell membrane and prevents the release of cytochrome c, which initiates apoptosis. (mlseducate.com)
  • MIF inhibited erythroid differentiation and hemoglobin production, and it antagonized the pattern of mitogen-activated protein kinase phosphorylation that normally occurs during erythroid progenitor differentiation. (rupress.org)
  • The color is consequence of the high content in hemoglobin , protein that is also responsible for the red color of the blood. (uvigo.es)
  • agitate is an distinguished chemical element of the hemoglobin protein organize which is intimately involved in the transport of oxygen. (blogspot.com)
  • Adult haemoglobin is a tetrameric haeme-protein. (blogspot.com)
  • On the other hand, S1P signals as extracellular mediator via five cell surface G-protein coupled receptors (GPCRs) termed S1P 1-5 . (abstract-management.de)
  • Either pharmacological reconstitution of FoxO activity using paclitaxel/ UCN-01, or reconstitution of the transcriptional activity of FoxO1 or FoxO3 by gene therapy, restored the physiologically quiescent vascular phenotype in vitro , linked to changes in cell cycle control and bone morphogenic protein receptor type 2 signaling, and reversed vascular remodeling and right-heart hypertrophy in vivo . (abstract-management.de)
  • Schroder,M, Friedl,P: Overexpression of recombinant human antithrombin III in Chinese hamster ovary cells results in malformation and decreased secretion of recombinant protein. (amazonaws.com)
  • Rapid duplication and loss of genes coding for the alpha chains of hemoglobin. (ijbmph.com)
  • There are two copies of the hemoglobin alpha gene ( HBA1 and HBA2 ), which each encode an α-chain, and both genes are located on chromosome 16. (rxharun.com)
  • Many mutated genes contribute to tumorigenesis by conferring on the cells enhanced self-renewal and proliferation capacities, 6 which represent a growth advantage over normal cells. (nature.com)
  • Likewise, embryonic hemoglobin such as hemoglobin Gower I (ζ 2 ε 2 ) and Gower II (α 2 ε 2 ) are produced in early life and switched to other Hb types during development. (intechopen.com)
  • While germ-line deletion of UFBP1 caused defective red blood cell development and embryonic lethality, somatic ablation of UFBP1 impaired production of mature red blood cells and other types of hematopoietic cells. (prolekare.cz)
  • It is well believed that human embryonic stem cells (hESCs [ 1 ]) and induced pluripotent stem cells (hiPSCs [ 2 ]) are of great potential use for tissue substitutes (for example, blood cells) and to cure various congenital disorders. (intechopen.com)
  • So far until now, in vitro hESC-derived blood cells possess phenotypical maturity and partial functions while still more or less share embryonic/fetal characteristics, differing greatly from their adult counterparts. (intechopen.com)
  • Another group has reported the creation of inducibly proliferating erythroid (IPE) progenitor cells from human embryonic stem (ES) cells by over-expression of both c-Myc and bcl-xl [ 16 ]. (biomedcentral.com)
  • Growth factors are peptides having low molecular weight and are found to be active in the stimulation of cell proliferation, regulation of embryonic development and cellular differentiation. (jacobspublishers.com)
  • To receive news and publication updates for Stem Cells International, enter your email address in the box below. (hindawi.com)
  • Various alterations in cell adhesion, metabolism, cytokine signaling, autophagy, and methylation patterns of tumor-derived mesenchymal stem cells have been demonstrated, contributing to the genesis of a leukemic permissive niche. (hindawi.com)
  • In addition, it has not been completely elucidated whether cancer-associated MSCs belong primarily to the abnormal clone or emerge after leukemic stem cell induced environmental damage. (hindawi.com)
  • A major focus of Dr. Abkowitz's research is hematopoietic stem cell (HSC) physiology. (uw.edu)
  • The process is regulated through a series of steps beginning with the hematopoietic stem cell. (mhmedical.com)
  • The precise molecular mechanism-either intrinsic to the stem cell itself or through the action of extrinsic factors-by which the stem cell becomes committed to a given lineage is not fully defined. (mhmedical.com)
  • non-responders need chronic transfusions or stem cell transplantation. (haematologica.org)
  • We overexpressed the constitutively active mutant STAT5A(1*6) in human cord blood CD34 + cells and evaluated the effects on the hematopoietic potential of stem cells in a variety of in vitro and in vivo systems. (rupress.org)
  • Our data indicate that a persistent activation of STAT5A in human hematopoietic stem and progenitor cells results in their enhanced self-renewal and diverts differentiation to the erythroid lineage. (rupress.org)
  • We found that depletion of UFBP1 led to elevated stress in the endoplasmic reticulum that in turn caused cell death of hematopoietic stem cells. (prolekare.cz)
  • EpoR expression can extend as far back as the hematopoietic stem cell compartment. (wikipedia.org)
  • Nonmyeloablative HLA-matched sibling allogeneic hematopoietic stem cell transplantation for severe sickle cell phenotype. (nih.gov)
  • Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. (biomedcentral.com)
  • Stem Cell Reports, 10(6):1908-1919. (uzh.ch)
  • The Rho GTPase Cdc42 regulates adhesion, migration, and homing, as well as cell cycle progression, of hematopoietic stem cells, but its role in multilineage blood development remains unclear. (bloodjournal.org)
  • In a classical view, the earliest cells in the hematopoietic hierarchy are the hematopoietic stem cells (HSCs). (bloodjournal.org)
  • Although almost all kinds of the mature blood cells can be generated from hESCs, there still lacks solid evidence for the generation of reconstituting hematopoietic stem cells (HSCs) from hESC or hiPSC. (intechopen.com)
  • Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells. (childrenshospital.org)
  • Production of human RBCs from hematopoietic stem cells has been achieved with 60,000 fold expansion from cord blood stem cells including safe transfusion into human patients, signifying the potential for the clinical translation of in vitro cultured RBCs [ 6 ]. (biomedcentral.com)
  • Treatment of human cells with ezatiostat leads to the activation of JNK, which promotes the growth and differentiation of hematopoietic stem cell precursors. (calcipotriol.net)
  • Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are treated with chemotherapy or other drugs, stem cell transplant, supportive care, and targeted therapy. (oncolink.org)
  • Myelodysplasia is a hematological disease in which genomic abnormalities accumulate in a hematopoietic stem cell leading to severe pancytopenia, multilineage differentiation impairment, and bone marrow (BM) apoptosis. (jci.org)
  • although the number of phenotypic hematopoietic stem cells (HSCs) in Setd2 -deleted mice is unchanged, functional assays, including serial BM transplantation, reveal that the self-renewal and competitiveness of HSCs are impaired. (nature.com)
  • Gene expression profile of Setd2 -deleted hematopoietic stem/progenitor cells (HSPCs) partially resembles that of Dnmt3a/Tet2 double knockout HSPCs, showing activation of the erythroid transcription factor Klf1-related pathway, which plays an important role in hematopoietic malignant transformation. (nature.com)
  • Hematopoietic homeostasis relies on a balance between hematopoietic stem cell (HSC) self-renewal and differentiation. (nature.com)
  • erythrocytes), which is the development from erythropoietic stem cell to mature red blood cell. (beringomega.org)
  • The only current potentially curative option, allogeneic hematopoietic stem cell transplant, is recommended for few patients. (biomedcentral.com)
  • Cytopenias are defined as a hemoglobin level below 10 g/dL, an absolute neutrophil count of less than 1,800/μL (see the Absolute Neutrophil Count calculator), and a platelet count below 100,000/μL. (medscape.com)
  • The immediate effects of EVI1 are hyperproliferation of BM cells and downregulation of EpoR and c-Mpl , which are important for terminal erythroid differentiation and platelet formation. (jci.org)
  • In a mouse model of MF, combined inhibition of the Hh and JAK pathways reduced JAK2 mutant allele burden, reduced bone marrow fibrosis, and reduced white blood cell and platelet counts. (biomedcentral.com)
  • Useful research indicated that lincRNA-EPS is certainly extremely induced in erythroid precursors if they begin synthesizing hemoglobin and various other lineage-specific proteins. (cylch.org)
  • In these experiments, the Company demonstrated HBG1/2 promoter-edited CD34+ cells robustly engrafted in mice without lineage skewing of red blood cell precursors. (ptcommunity.com)
  • Following lineage commitment, hematopoietic progenitor and precursor cells come increasingly under the regulatory influence of growth factors and hormones. (mhmedical.com)
  • Identification and characterization of novel full-length cDNAs expressed during hematopoietic lineage-specific differentiation of cultured human peripheral blood mononuclear cells. (nih.gov)
  • The active mitotic activity seen in the bone marrow is critical for the virus to replicate, thus the clinical manifestations often observed involving red cell lineage. (clinicaladvisor.com)
  • Transfer of 4-hydroxynonenal, a inhibitory hemozoin (HZ) product, from HZ or HZ-laden phagocytes to developing human erythroid cells. (biomedcentral.com)
  • It is also inconsistent with the low levels of EPO receptors on those cells. (wikipedia.org)
  • Overexpression of mouse Tfr1 , mouse Tfr2 , and zebrafish tfr1b partially rescued hypochromia in cia embryos, establishing that each of these transferrin receptors are capable of supporting iron uptake for hemoglobin production in vivo. (biologists.org)
  • Transferrin donates its Fe to cells by binding to specific Tf receptors (TfR) on the cell membrane. (allindianpatents.com)
  • Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. (plos.org)
  • Via activation of S1P 2 receptors, S1P concurrently activates both Rho kinase signaling and - via phospholipase C - TRPC6 which conjointly cause smooth muscle cell contraction. (abstract-management.de)
  • In addition to qualitative regulation of signaling pathways, quantitative control may be essential to control appropriate cell numbers in peripheral blood. (ox.ac.uk)
  • This receptor is also found in a large number of tissues such as bone marrow cells and peripheral/central nerve cells, many of which activate intracellular biological pathways upon binding with Epo. (codagu.com)
  • It is known that EpoR can activate mitogenic signaling pathways and can lead to cell proliferation in erythroleukemic cell lines in vitro, various non-erythroid cells, and cancer cells. (wikipedia.org)
  • How these disturbed pathways fail to produce sufficient blood cells and lead to leukemogenesis are not understood. (haematologica.org)
  • Forkhead box O (FoxO) transcription factors are key regulators of cellular proliferation, migration, differentiation and apoptosis by modulating and integrating multiple signaling pathways. (abstract-management.de)
  • Treatment of septic patients also aims at optimizing the delivery of oxygen to tissues in order to alleviate cellular hypoxia and the progression of cell dysfunction, in an attempt to avoid or attenuate the development of multiple organ dysfunction syndrome [ 1 ]. (biomedcentral.com)
  • Erythrocytes or red blood cells (RBC) play a crucial role in oxygen carrying and transportation. (intechopen.com)
  • Iron acquisition by developing erythroid cells is necessary to produce hemoglobin, which allows red blood cells to deliver oxygen to body tissues in exchange for carbon dioxide. (biologists.org)
  • The energy used by neurons is derived largely from tissue oxidative metabolism, and neural hyperactivity and cell death are reflected by corresponding changes in cerebral oxygen metabolism (CMRO 2 ). (jove.com)
  • Continuous-wave near-infrared spectroscopy (CWNIRS) provides non-invasive and non-ionizing radiation measures of hemoglobin oxygen saturation (SO 2 ) as a surrogate for cerebral oxygen consumption. (jove.com)
  • Subject to capillary deformation, red blood cells can release ATP and nitric oxide with a vasodilator role, and upon release of hemoglobin-bound oxygen, they release S-nitroso-thiols, which also have a vasodilator role ( 5-7 ). (spandidos-publications.com)
  • The symptoms which are common to all types of anaemia occur because of the impaired ability of the red blood cells to transport oxygen around the body. (enetmd.com)
  • A severe reduction in haemoglobin can result in in shortness of breath on exertion, dizziness because of of reduced amounts of oxygen reaching the brain, angina pectoris (chest pain due to impaired oxygen supply to the heart muscle), and palpitations as the heart works harder to compensate. (enetmd.com)
  • The excess β chains form unstable tetramers (called hemoglobin H or HbH of 4 beta chains), which have abnormal oxygen dissociation curves. (rxharun.com)
  • The role of red blood cells is to carry oxygen. (mlseducate.com)
  • Just like anything in the body, this is tightly regulated by a mechanism that monitors whether or not there is adequate oxygen getting to tissues and other cells. (mlseducate.com)
  • When EPO levels are low, because there is adequate oxygen delivery the older FASL bearing cells cross-link with earlier FAS precursors which stimulates apoptosis. (mlseducate.com)
  • Parvovirus B19 infection occurs via the globoside (P antigen) receptor, the main glycolipid of erythroid cells, which induces apoptosis. (springeropen.com)
  • PB19 infection occurs via the globoside (P antigen) receptor, the main glycolipid of erythroid cells, and induces apoptosis. (springeropen.com)
  • The antioxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress-induced cell death. (nih.gov)
  • ERFE is probably not the sole erythroid regulator of hepcidin because adult Erfe-deficient mice had normal hematologic and iron parameters. (bloodjournal.org)
  • In mammalian cells, Cdc42 has been shown to be a critical regulator of a broad range of cellular functions including actin cytoskeletal organization, gene transcription, cell proliferation, and differentiation. (bloodjournal.org)
  • Neutral sphingomyelinase, which generates ceramide from sphingomyelin at the outer leaflet of the cell membrane, mediates hypoxic pulmonary vasoconstriction (HPV) by promoting the recruitment of transient receptor potential canonical 6 (TRPC6) Ca 2 channels that are essential for HPV to caveolae in a process that surprisingly is dependent on cystic fibrosis transmembrane conductance regulator (CFTR). (abstract-management.de)
  • The red blood cell precursors from bone marrow edited at the BCL11A e site had lower productive editing rates compared to other lineages and showed increased level of apoptosis, or programmed cell death, in erythroid culture compared to HBG1/2 promoter-edited cells. (ptcommunity.com)
  • We are encouraged by these preclinical results demonstrating cells edited at the HBG1/2 promoters repopulated all lineages of the blood system including, importantly, the red blood cell precursors. (ptcommunity.com)
  • Typically, blood transfusion was given to older patients with a higher rate of malignancy and lower hemoglobin levels. (biomedcentral.com)
  • While hemoglobin concentration on admission had strong correlation with in-hospital mortality (O.R-0.83 [95 % C.I. 0.74-0.92], blood transfusion was not found to be an independent predicting factor for mortality. (biomedcentral.com)
  • Several mechanisms contribute to acute reduction in hemoglobin levels in the setting of sepsis, including reduced production of red blood cells induced by the systemic inflammatory response, as well as increased destruction of red cells due to hemolysis and bleeding. (biomedcentral.com)
  • Based on this notion, maintenance of adequate blood hemoglobin level was suggested as one of the tools to diminish sepsis induced tissue damage. (biomedcentral.com)
  • MSCs are adult multipotent cells that can be isolated from the bone marrow, umbilical cord blood, placenta, or adipose tissue [ 6 ] and represent fundamental actors in the formation, organization, and function of the hematopoietic niche [ 7 - 9 ]. (hindawi.com)
  • HSCs, the parent cells that establish and maintain blood cell production, reside in niches within marrow and are infrequent ( (uw.edu)
  • Low levels of EPO (around 10 mU/mL) are constantly secreted sufficient to compensate for normal red blood cell turnover. (wikipedia.org)
  • We show that cia encodes tfr1a , which is specifically expressed in the developing blood and requisite only for iron uptake in erythroid precursors. (biologists.org)
  • The erythron is a dynamic organ made up of a rapidly proliferating pool of marrow erythroid precursor cells and a large mass of mature circulating red blood cells. (mhmedical.com)
  • Studies in blood samples to characterize red cell acyl CoA synthetase activity in combination with LACS5 sequence identity may shed light on the altered utilization of fatty acids in the brain of these patients. (chori.org)
  • In this issue of Blood , Kautz et al 1 show that the ablation of the erythroid-derived factor erythroferrone (ERFE), which has been shown to be highly expressed in β-thalassemic mice, 2 restores hepcidin levels and corrects iron overload. (bloodjournal.org)
  • Macrophages tightly control the production and clearance of red blood cells (RBC). (frontiersin.org)
  • During their development and mature life, red blood cells (RBC) interact numerous times with macrophages, first during their development in the bone marrow, later in the blood stream with macrophages in the liver and spleen. (frontiersin.org)
  • It is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. (codagu.com)
  • Also called hematopoietin or hemopoietin , it is produced by the peritubular capillary endothelial cells in the kidney, and is the hormone that regulates red blood cell production. (codagu.com)
  • History In 1906, Paul Carnot, a professor of medicine in Paris, and his assistant DeFlandre proposed the idea that hormones regulate the production of red blood cells. (codagu.com)
  • After conducting experiments on rabbits subject to bloodletting, Carnot and DeFlandre attributed an increase in red blood cells in rabbit subjects to a hemotopic factor called hemopoietin. (codagu.com)
  • Further studies investigating the existence of EPO by Reissman, and Erslev demonstrated that a certain substance circulated in the blood is able to stimulate red blood cell production and increase hematocrit. (codagu.com)
  • Haematologist John Adamson and nephrologist Joseph W. Eschbach looked at various forms of renal failure and the role of the natural hormone EPO in the formation of red blood cells. (codagu.com)
  • Similar results have been described in human CD34 + cells isolated from cord blood (CB), although high expression levels of HOXB4 resulted in a profound in vivo competitive growth advantage of HSCs, but an impairment of lymphomyeloid differentiation ( 8 ). (rupress.org)
  • Furthermore, UFBP1 deficiency diminished expression of key transcription factors essential for red blood cell development. (prolekare.cz)
  • In addition, some evidence on macrocytosis in hypoxic stress (when Epo can increase 1000-fold) suggests that mitosis is actually skipped in later erythroid stages, when EpoR expression is low/absent, in order to provide emergency reserve of red blood cells as soon as possible. (wikipedia.org)
  • Blood Cells Mol Dis (2019 Jul) 77:12-16. (nih.gov)
  • The total reduction of red blood cell (RBC) count is associated with poor prognosis in these patients. (biomedcentral.com)
  • This study evaluated the impact of chemotherapies on the parameters belonging to the red blood cell series in the hemogram and aimed to identify some particular evolution profiles. (spandidos-publications.com)
  • The average lifespan of an erythrocyte is 120 days and, every day, 200 billion red blood cells are released into circulation and 'withdrawn' respectively ( 1 ). (spandidos-publications.com)
  • This is when there are blood group incompatibilities between a mother and offspring (NI) or between a recipient and a donor ( transfusion reaction , the most serious of which is when the recipient rapidly lyses donor cells). (eclinpath.com)
  • Splitting of circulating red blood cells as -mechanism of erythrocyte maturation in developing zebrafish, chick and mouse embryos. (uzh.ch)
  • Squeezing for life - properties of red blood cell deformability. (uzh.ch)
  • The red blood cells on the move! (uzh.ch)
  • 11 , 12 In mature blood cells, Cdc42 has been found to regulate macrophage chemotaxis, 13 monocyte transmigration, 14 lymphocyte polarization and directional migration, 15 , 16 and neutrophil migration. (bloodjournal.org)
  • On the other hand, functionally matured blood cells derived from hESC/hiPSCs are expected to be widely used for clinical cellular therapies. (intechopen.com)
  • They may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate. (wikipedia.org)
  • Being anaemic means that there is a problem with the red blood cells. (enetmd.com)
  • In anaemia the level or concentration of haemoglobin in red blood cells is reduced. (enetmd.com)
  • There is a balance between red cell production by the bone marrow and destruction of old red blood cells by the spleen. (enetmd.com)
  • The healthy body maintains a constant level of red blood cells and haemoglobin. (enetmd.com)
  • This increased loss of red cells is caused either by blood loss or or premature destruction of red cells (known medically as haemolysis). (enetmd.com)
  • For example, some degree of jaundice occurs in most types of haemolytic anaemia because the high rate of destruction of red blood cells leads to an increased level of the yellow pigment bilirubin (produced by the breakdown of the haemoglobin in red cells) in the blood. (enetmd.com)
  • A bone marrow sample or biopsy (removal of a small sample of bone marrow for analysis) may be needed to decide if red blood cell production is defective. (enetmd.com)
  • After emergency transfusion of eight units of red blood cells, her hemoglobin level recovered to 8.4 g/dL. (springeropen.com)
  • they precipitate intracellularly, resulting in hemolysis, premature destruction (by apoptosis) of red blood cell (RBC) precursors in the bone marrow, and a short life-span of mature RBCs in the circulation. (rxharun.com)
  • However, excess α-chains can form insoluble aggregates inside red blood cells. (rxharun.com)
  • The spleen becomes enlarged as it removes damaged red blood cells from the circulation. (rxharun.com)
  • Both BFU-E and CFU-E are red blood cell progenitor cells that develop into the pronormoblast, which is the first morphologically identifiable red blood cell precursor. (mlseducate.com)
  • The normal death signal consists of a death receptor being FAS, on the membrane of the earliest red blood cell precursors (CFU-Es/BFU-Es), and FASL ligand on the maturing red blood cells precursors. (mlseducate.com)
  • It also stimulates the production of egress-promoting surface molecules within the bone marrow which allow the red blood cells to flow through the marrow easier. (mlseducate.com)
  • A robust scalable method for producing enucleated red blood cells (RBCs) is not only a process to produce packed RBC units for transfusion but a potential platform to produce modified RBCs with applications in advanced cellular therapy. (biomedcentral.com)
  • Red blood cells (RBCs) are an ideal platform for novel cellular therapies as they are physically stable, universally biocompatible (type O, Rhesus factor negative), contain no nucleus, and can potentially be packed and coated with biologically active molecules. (biomedcentral.com)
  • E rythrocytes, also known as red blood cells, are the most abundant and the smallest (at least in mammals) blood cells. (uvigo.es)
  • Patients who fail steroid treatment (non-responders or those in whom an unacceptably high steroid dose is necessary to maintain the hemoglobin) should be weaned off steroids and will require regular blood transfusions at approximately 4 to 6 week intervals. (renalandurologynews.com)
  • Normal p arnthood consists of three types of tide rip cells white blood cells (leucocytes), platelets and red blood cells (erythrocytes). (blogspot.com)
  • They ar carried to the developing liver by the blood where they form mature red blood cells that argon required to meet the metabolic demands of the foetus. (blogspot.com)
  • The life of a red blood cell is about 127 twenty-four hour periods or 4 months (Shemin and Rittenberg, 1946 Kohgo et al. (blogspot.com)
  • The convention blood haemitinoglobin concentration is dependent on age and sex, and, according to the World health Organisation (WHO) Expert Committee Report, anaemia results when the blood concentration of haemoglobin falls be lower-ranking 130 g/L in men or 120 g/L in n on-pregnant women (WHO, 1968). (blogspot.com)
  • However, the reference prevail of haemoglobin concentration in blood could vary depending on the ethnicity, age, sex, env pushmental somas and food habits of the macrocosm analysed. (blogspot.com)
  • This aggregation leads to deformation of the red blood cell making it relatively inflexible and restrict its movement in the hairlike beds. (blogspot.com)
  • regular clogging of the capillary beds damages the kidneys, heart and lungs go the constant destruction of the sickled red blood cells triggers chronic anaemia and episodes of hyperbilirubinaemia.Fanconi anaemia (FA) is an autosomal recessive condition, and the most common type of inherited bone marrow failure syndrome. (blogspot.com)
  • The condition results in diminished haemoglobin concentrations on account of shortened red blood cell lifespan (Sokol et al. (blogspot.com)
  • Each unit of transfused packed red blood cells contains 200 to 250 mg elemental iron. (ashpublications.org)
  • A second compound in a new class of activin receptor proteins, ACE-536, is under investigation to treat beta-thalassemia, a blood disorder characterized by reduced hemoglobin production. (thefreedictionary.com)
  • 2006 ). More recently, we have demonstrated that morpholino knockdown of Etv7 in zebrafish leads to loss of hemoglobin-containing red blood cells by repression of the lanosterol synthase ( lss ) gene, indicating that in fish ETV7 is indispensable for normal red blood cell development (Quintana et al. (springer.com)
  • Other tissues which are major users of iron include the muscles (2-3%) where it is present in the haem group of myoglobin, tissue macrophages (5%) involved in red blood cell (RBC) recycling and liver hepatocytes (20%) where excess iron is stored within ferritin. (mdpi.com)
  • The bone marrow of essentially all the bones produces red blood cells until a person is around five years old. (beringomega.org)
  • the vertebrae, sternum, pelvis and ribs, and cranial bones continue to produce red blood cells throughout life. (beringomega.org)
  • In 1905, Paul Carnot proposed the idea that a hormone regulates the production of red blood cells. (beringomega.org)
  • tfr1b morphants exhibited growth retardation and brain necrosis, similar to the central nervous system defects observed in the Tfr1 null mouse, indicating that tfr1b is probably used by non-erythroid tissues for iron acquisition. (biologists.org)
  • In mammals, O 2 is transported to tissues bound to the hemoglobin contained within circulating red cells. (mhmedical.com)
  • Muscular dystrophies are often caused by mutations in cytoskeletal proteins that render cells more susceptible to strain-induced injury in mechanically active tissues such as skeletal or cardiac muscle. (jci.org)
  • It is ubiquitously expressed in multiple tissues and organs with high- level expression in secretory cells [ 7 ]. (prolekare.cz)
  • IntroductionAnaemia is a syndrome characterised by a lack of healthy rosy-cheeked daub prison jail mobile phones or hemoglobin wishing in the trigger-happy melodic line cells, resulting in short(p) type O supply to the tissues. (blogspot.com)
  • Also, the valine for glutamic acid heir causes the haemoglobin tetramers to aggregate into arrays upon deoxygenation in the tissues. (blogspot.com)
  • Hence, it can be said that growth factors exhibit their effects on various types of cells and initiate a cascade of cellular functions in different types of tissues. (jacobspublishers.com)
  • [7] Tissue hypoxia triggers endogenous EPO production when hemoglobin (Hb) falls below 12 g/dL. (mjhid.org)
  • Taken together, these data show that zebrafish tfr1a and tfr1b share biochemical function but have restricted domains of tissue expression, and establish a genetic model to study the specific function of Tfr1 in erythroid cells. (biologists.org)
  • Activins are involved in all stages of the cell cycle: proliferation, differentiation, metabolism, homeostasis, and death (apoptosis), as well as immune response and tissue repair-activins A and B are highly expressed during wound repair and healing, and have yin-yang relationship with inhibin. (thefreedictionary.com)
  • Importantly, the ETV7 expression pattern in hematopoietic cells of ETV7Tg + /WT mice was evaluated by qRT-PCR and was very similar to that in human hematopoietic cells, suggesting that our ETV7Tg + /WT mouse properly reflects the tissue-specific expression of human ETV7. (springer.com)
  • The progenitor cells undergo a marked reduction in cell volume starting at 900 fl for precursors and ending with 95 fl for mature erythrocytes. (spandidos-publications.com)
  • Initial analysis of Gadd34 -null mice revealed several significant findings, including hypersplenism, decreased erythrocyte volume, increased numbers of circulating erythrocytes, and decreased hemoglobin content, resembling some thalassemia syndromes. (asm.org)
  • Nonetheless, erythrocytes are really stable cells because of their cell features. (uvigo.es)
  • The plasma membrane of erythrocytes show a cholesterol proportion above 30 %, higher than in an average cell, that makes plasma membrane less fluid, more stiff and more hydrophobe (less permeable). (uvigo.es)
  • Increased proliferation and migration and resistance to apoptosis of pulmonary vascular cells play a major role in pathologic remodeling processes underlying different variants of PH. (abstract-management.de)
  • We discovered that UCA1 expression is dynamically regulated during human erythroid maturation, with a maximal expression in proerythroblasts. (nature.com)
  • A diagnosis of MDS-MLD requires that dysplastic features be present in more than 10% of cells from two or more lineages. (medscape.com)
  • The alpha (HBA) and beta (HBB) loci determine the structure of the 2 types of polypeptide chains in adult hemoglobin, Hb A. The normal adult hemoglobin tetramer consists of two alpha chains and two beta chains. (genecards.org)
  • Adult hemoglobin is composed of two alpha (α) and two betas (β) polypeptide chains. (rxharun.com)
  • Hallenbeck first defined the potential participation of leukocyte activation in a restricted form of problems for the central anxious program (CNS).11 Subsequently del Zoppo confirmed the first appearance of PMN leukocytes within hours from the onset the focal ischemia (Fig. 1).3 Several research followed which verified the individuals in leukocyte-vascular adherence and "no-reflow " leukocyte transmigration and activation and receptor exposure on both endothelial cells and PMN leukocytes. (bostonscienceandengineeringlectures.com)
  • Included in these are a humanized monoclonal antibody (MoAb) against ICAM-1 portrayed on turned on endothelial cells a humanized MoAb against PMN leukocyte Compact disc18 the recombinant neutrophil inhibitory aspect (rNIF) that prevents neutrophil adhesion and an inhibitor from the action from the interleukin-1β (IL-1β) the interleukin-1 CCT128930 receptor antagonist (IL-1ra). (bostonscienceandengineeringlectures.com)
  • CD105 is highly expressed on endothelial cells and promotes angiogenesis during wound healing, infarcts and in a wide range of tumours and its gene expression is stimulated by hypoxia. (novusbio.com)
  • CD105 prevents apoptosis in hypoxic endothelial cells and also antagonises the inhibitory effects of TGFb-1 on vascular endothelial cell growth and migration. (novusbio.com)
  • Akassoglou K, Yu WM, Akpinar P, Strickland S (2002) Fibrin inhibits peripheral nerve remyelination by regulating Schwann cell differentiation. (springer.com)
  • Recent reports suggest that signaling through EpoR may be important in breast tumorigenesis ( 3 ) and may decrease hypoxia-induced apoptosis in vitro ( 10 ). (aacrjournals.org)
  • Preclinical in vitro and in vivo assays using cell lines and primary leukemia patient samples were used to evaluate antileukemic effects of UNC2025. (aacrjournals.org)
  • Pharmacological inhibition and genetic ablation of FoxO1 in smooth muscle cells and FoxO3 in fibroblasts reproduced PH features in vitro and in vivo . (abstract-management.de)
  • The loss of GMPs is likely due to increased apoptosis and increased phagocytosis, the latter due to the up-regulation of cell surface calreticulin, a prophagocytic marker. (stanford.edu)
  • it allows early release of reticulocytes from the bone marrow, prevents apoptosis, and reduces the time needed for cells to mature in the bone marrow before release into the periphery. (mlseducate.com)
  • Arousal of filtered N cells using the proteins kinase C activator phorbol 12-myristate 13-acetate (PMA) and the calcium mineral ionophore ionomycin along with monensin added to stop proteins release (collectively, PIM) lead in build up of cytoplasmic IL-10 at adequate amounts to enable recognition of uncommon IL-10-skilled spleen N cells 6385-02-0 manufacture by immunofluorescence yellowing. (bus2226w16.com)
  • The first cistronration of erythrocyte precursors in the developing foetus ar realised in the yolk sac. (blogspot.com)
  • Signs and symptoms of pediatric acute myelocytic leukemia (AML) can be divided into the following: (1) those caused by a deficiency of normally functioning cells, (2) those due to the proliferation and infiltration of the abnormal leukemic cell population, and (3) constitutional symptoms. (medscape.com)
  • Setd2 deficiency also induces DNA replication stress in HSCs, as reflected by an activated E2F gene regulatory network and repressed expression of the ribonucleotide reductase subunit Rrm2b, which results in proliferation and cell cycle abnormalities and genomic instability, allowing accumulation of secondary mutation(s) that synergistically contributes to tumorigenesis. (nature.com)
  • Hemoglobin H (HbH) disease is a form of alpha thalassemia with one out of four alpha chains present. (clinicaladvisor.com)
  • HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update. (ijbmph.com)
  • Typical beta-thalassemia carriers are identified by analysis of RBC indices, which shows microcytosis (low MCV) and reduced content of Hb per red cell (low MCH), and by qualitative and quantitative Hb analysis, which displays the increase of HbA2. (rxharun.com)
  • Viability of beta-thalassemia /HbE erythroid progenitor cells in the presence of IL-3 was higher than that of nonsupplemented cells . (bvsalud.org)
  • Percent apoptosis of erythroid progenitor cells from splenectomized beta-thalassemia /HbE subjects treated with RO-318220 was higher than those of nonsplenectomized beta-thalassemia /HbE and healthy subjects . (bvsalud.org)
  • Treatment with U-73122 resulted in enhanced percent apoptotic cells from normal and beta-thalassemia /HbE subjects. (bvsalud.org)
  • Thalassemia is an inherited disease with multiple genetic forms, including α-thalassemia, β-thalassemia, hemoglobin E/β-thalassemia, and others. (ashpublications.org)
  • EPO is able to subdue apoptosis by stimulating the more mature precursors to be released from the marrow, especially in times of hypoxia. (mlseducate.com)
  • In chronic hypoxia, prolonged stimulation of S1P 2 promotes lung vascular remodeling by stimulating both smooth muscle cell proliferation as well as hypertrophy. (abstract-management.de)
  • However, relatively little is known about EpoR signaling in tumor cells. (aacrjournals.org)
  • Sodium phenylbutyrate (PB) demonstrates potent differentiating capacity in multiple hematopoietic and solid tumor cell lines. (aacrjournals.org)
  • It should be noted that tumor markers, such as PSA, might not be the most accurate measurements of progressive disease in patients treated with PB, as a rise in tumor markers may signal cell differentiation rather than disease progression. (aacrjournals.org)
  • The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. (plos.org)