AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPsychiatry and PsychologyPhenomena and ProcessesDisciplines and OccupationsAnthropology, Education, Sociology and Social PhenomenaInformation ScienceNamed GroupsHealth Care
Hematopoietic Stem CellsHematopoietic Stem Cell TransplantationStem CellsHematopoiesisStem Cell TransplantationCell DifferentiationEmbryonic Stem CellsCell LineageStem Cell NicheHematopoietic Stem Cell MobilizationTransplantation, HomologousAntigens, CD34Adult Stem CellsBone Marrow CellsPluripotent Stem CellsColony-Forming Units AssayInduced Pluripotent Stem CellsMice, Inbred C57BLStem Cell FactorMultipotent Stem CellsFlow CytometryGraft vs Host DiseaseCells, CulturedTransplantation ConditioningBone MarrowFetal BloodCell ProliferationCell SeparationBone Marrow TransplantationMesonephrosTransplantation, AutologousHematopoietic SystemHematologic NeoplasmsNeural Stem CellsMesenchymal Stromal CellsMice, SCIDMesenchymal Stem Cell TransplantationFetal Stem CellsCloning, OrganismHybrid CellsTransplantation ChimeraNuclear Transfer TechniquesProto-Oncogene Proteins c-kitCell Culture TechniquesNuclear ReprogrammingLentivirusCord Blood Stem Cell TransplantationMice, Inbred NODWhole-Body IrradiationGraft SurvivalEmbryo, MammalianTransduction, GeneticChimerismLeukemiaGenetic VectorsRetroviridaeMice, TransgenicMyeloid Progenitor CellsGranulocyte Colony-Stimulating FactorPeripheral Blood Stem Cell TransplantationMice, KnockoutTissue DonorsLymphopoiesisAntigens, CDNeoplastic Stem CellsCell DivisionGene Expression Regulation, DevelopmentalHematopoiesis, ExtramedullaryTime FactorsRadiation ChimeraCell CountSignal TransductionOctamer Transcription Factor-3GonadsCell LinePhenotypeReverse Transcriptase Polymerase Chain ReactionRegenerationGreen Fluorescent ProteinsStem Cell ResearchGenetic TherapyStromal CellsGene Expression RegulationAntigens, CD38Antigens, LyThrombopoietinGerm CellsCell CycleBusulfanHistocompatibility TestingCoculture TechniquesAntigens, Thy-1Clone CellsCell SurvivalTranscription FactorsHistocompatibilityLymphoid Progenitor CellsModels, BiologicalFetusHematologic Diseases
TransplantationAcquisition of somaticMutationProgenitorsHematopoiesis of indeterminate potentialProgenitor cellTissuesHuman hematopoietic cellsLineagesVariantsMutations that occurPrecursorsPromote clonal expansionLead to clonal expansionMutant hematopoieticGenesHSCsAcute myeloidEmbryonic stemGeneticsDNMT3AGermline geneticMalignantSelf-renewalProliferation and differentiationTransplantDonorTET2Play a pivotal roleLeukemiaPopulationsAbnormalLineageTranscriptionalGene expressionRegulatorBlood cellsPathwaysPIGAPatients2016TherapiesPeripheralMicroenvironmentOutcomeChronicDifferentiateTumorsDifferentiation capacityStromal
Transplantation18
Acquisition of somatic4
  • Clonal hematopoiesis (CH) is defined as the acquisition of somatic mutations in blood cells and is associated with smoking and exposure to genotoxic stimuli. (nature.com)
  • It involves the acquisition of somatic mutations in hematopoietic stem cells or early progenitor cells, leading to the expansion of a clone of cells with these mutations. (peoplebeatingcancer.org)
  • MDS is associated with serial acquisition of somatic variants, which over decades may result in progressive dysplasia. (standardofcare.com)
  • Risk increases with age due to the acquisition of somatic mutations that can promote clonal expansion and dominance of a particular hematopoietic stem cell, and possibly due to exposure to environmental toxins such as benzene, radiation, and chemotherapeutic agents (particularly long or intense regimens and those involving alkylating agents, hydroxyurea , and/or topoisomerase inhibitors). (msdmanuals.com)
Mutation18
  • VEXAS syndrome is an adult-onset autoinflammatory disease primarily affecting males, caused by a somatic mutation of the UBA1 gene in hematopoietic progenitor cells. (wikipedia.org)
  • Based on the variation in the frequencies of different immune cells exhibiting the DNMT3A mutation, in-depth analyses were performed for these subsets of immune cells. (news-medical.net)
  • Paroxysmal nocturnal hemoglobinuria or PNH is a rare benign clonal acquired hematopoietic stem-cell (HSC) disorder that results from somatic mutation of the X- linked phosphatidylinositol glycan class A gene known as the PIGA gene. (aacc.org)
  • Whole genome sequence data from Iceland and the UK Biobank, combined with a unique somatic mutation Barcoding strategy, was used to investigate clonal hematopoiesis at the population scale. (decode.com)
  • Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation. (ox.ac.uk)
  • Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. (biomedcentral.com)
  • All GS-2 iPSC clones displayed a normal karyotype (46XX or 46XY) and were shown to express the same RAB27A gene mutation that was present in the original somatic donor cells. (biomedcentral.com)
  • 1. Development of genetically engineered models of myeloid malignancies in order to study the impact of specific driver mutation(s) on the establishment, evolution and propagation of leukaemic stem cells. (ox.ac.uk)
  • Characterized by excessive, abnormal white blood cell (granulocyte) production and the presence of the Philadelphia chromosome/BCR-ABL mutation, chronic myeloid leukemia (CML) is a slow-growing cancer of the blood-forming tissue (bone marrow). (oncomine.com)
  • Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell caused by a leukemogenic mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. (peoplebeatingcancer.org)
  • However, much remains unknown about how specific therapy exposures shape the evolution and somatic mutation profiles of CH and how this complex interplay leads to the development of overt leukemia. (harvard.edu)
  • Paroxysmal nocturnal hemoglobinuria (PNH) was previously classified as purely an acquired hemolytic anemia due to a hematopoietic stem cell mutation defect. (medscape.com)
  • The common denominator in the disease, a biochemical defect, appears to be a genetic mutation leading to the inability to synthesize the glycosyl-phosphatidylinositol (GPI) anchor that binds these proteins to cell membranes. (medscape.com)
  • Due to its location on the X chromosome, and due to X inactivation in female somatic cells, only one mutation is required in either males or females to abolish the expression of GPI-linked proteins. (medscape.com)
  • Most type II PNH cells (total lack of GPI-linked protein) are due to a frame shift mutation occurring in the early hematopoietic progenitor cells, resulting in same mutation in all blood cell lines. (medscape.com)
  • The mutation occurs in hematopoetic stem cells capable of self renewal and additional mutations are associated with clonal progression may occur in progenitor cells conferring a self renewal capability. (standardofcare.com)
  • Somatic mutation is not a static process in myelodysplastic syndrome and additional mutations will accumulate leading to more profound phenotypic worsening cytopenias, and approximately 30% of patients will eventually experience progression to secondary AML. (standardofcare.com)
  • The paradox is that the mutation provides advantage at the stem cell level and progenitor cells, with a disadvantage at the level of hematopoietic precursors. (standardofcare.com)
Progenitors3
  • In this assay hematopoietic cells are cultured in MyeloCult™ medium with supportive human or mouse stromal cell layers and tested for their ability to generate myeloid clonogenic progenitors for several weeks as assayed by replating the cells in a colony-forming unit (CFU) assay using MethoCult™ medium. (stemcell.com)
  • Establish stromal cell layers and culture hematopoietic progenitors in "Dexter-type" long-term bone marrow cultures. (stemcell.com)
  • They are commonly expressed in pluripotent embryonic stem cells, germ cells, certain committed progenitors, and cancer cells 18 . (atlasantibodies.com)
Hematopoiesis of indeterminate potential5
  • Characteristics of Clonal Hematopoiesis (CH) Mutations - a) We identified somatic mutations in known clonal hematopoiesis of indeterminate potential (CHIP) driver genes using peripheral blood mononuclear cells isolated from 14 astronauts who flew short space Shuttle missions lasting a median of 12 days between 1998-2001. (spaceref.com)
  • However, the frequency of the somatic mutations in the genes that the researchers assessed was less than two percent, the technical threshold for somatic mutations in hematopoietic stem cells to be considered clonal hematopoiesis of indeterminate potential (CHIP). (spaceref.com)
  • In a recent study published in the Nature Cardiovascular Research , researchers used single-cell sequencing methods to examine the cell-intrinsic effects of hematopoietic stem cells with somatic mutations that result in clonal hematopoiesis of indeterminate potential (CHIP), in circulating cells from heart failure patients. (news-medical.net)
  • Clonal hematopoiesis of indeterminate potential (CHIP) is a condition characterized by the presence of genetically distinct populations of blood cells, specifically in the hematopoietic (blood-forming) system. (peoplebeatingcancer.org)
  • Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. (biomedcentral.com)
Progenitor cell2
  • Our particular focus is to refine risk stratification of patients using these molecular markers and also to gain a better understanding of how germline mutations might disrupt stem/progenitor cell populations to promote the development of myeloid malignancies. (ox.ac.uk)
  • Moreover, mice treated with WTC particulate matter developed an increased burden of mutations in hematopoietic stem and progenitor cell compartments. (nature.com)
Tissues8
  • Overall, we observe that germline genetic variation shapes hematopoietic stem cell function, leading to CHIP through mechanisms that are specific to clonal hematopoiesis as well as shared mechanisms that lead to somatic mutations across tissues," co-senior authors Sekar Kathiresan and Pradeep Natarajan, both of the Broad, and their colleagues wrote in their paper. (genomeweb.com)
  • Among all cancerous cells, a few act as stem cells that reproduce and sustain the tumor, much like stem cells normally renew and sustain our organs and tissues. (atlasantibodies.com)
  • In this study, we compared hematopoietic differentiation capacity of 35 human iPSC lines derived from four different tissues and four embryonic stem cell lines. (nih.gov)
  • Many studies have shown the utility of embryonic or adult stem cells for forming teeth and for regeneration of bone and soft tissues. (bvsalud.org)
  • Adult stem cells are classified as pluripotent and are undifferentiated cells that remain quiescent in tissues until stimulated, when they can create cell types that are compatible with the tissue in which they reside. (bvsalud.org)
  • Additionally, they can form specialized cell types from other tissues if they are transplanted 6 . (bvsalud.org)
  • Stromal cells are a mixed population that can create bone, cartilage and fat and also fibrous and connective tissues. (bvsalud.org)
  • The key functions of adult stem cells are to maintain and repair the specific tissues where they reside (e.g. skin or blood). (bvsalud.org)
Human hematopoietic cells1
  • These findings identify a new intrinsic, pervasive, and progressive aging-related alteration in the biological and signaling mechanisms required to drive the proliferation of very primitive, normal human hematopoietic cells. (ashpublications.org)
Lineages6
  • On bone marrow examination, people with the disease exhibit abnormal vacuoles in precursor cells of the myeloid and erythroid lineages. (wikipedia.org)
  • The variation among induced pluripotent stem cells (iPSCs) in their differentiation capacity to specific lineages is frequently attributed to somatic memory. (nih.gov)
  • The process of differentiation in stem cells involves selective development of immature cells to committed and fully mature cells of various lineages. (justia.com)
  • The natural process of blood cell formation, hematopoietic stem cell differentiation, and generation of myeloid and lymphoid cell lineages. (oncomine.com)
  • Myeloproliferative neoplasms present with the clonal proliferation of 1 or more myeloid cell lineages.10 The role of genetic and genomic aberrations in pathogenesis has been well documented for these disorders. (oncomine.com)
  • By definition, adult stem cells are capable of differentiation into at least two lineages and have the property of self-renewal. (bvsalud.org)
Variants5
  • In people with PNH, variants of the PIGA gene occur during a person's lifetime and are present only in certain cells. (medlineplus.gov)
  • These changes, which are called somatic variants, are not inherited. (medlineplus.gov)
  • b) Number of somatic nonsynonymous single nucleotide variants (SNVs) in CHIP-driver genes harbored per subject. (spaceref.com)
  • The researchers homed in on a set of about two dozen likely causal variants, which they hypothesized affects a TET2 enhancer in hematopoietic stem cells. (genomeweb.com)
  • Recent Findings: Emerging evidence suggests that development of t-MN is the result of complex interactions including generation of somatic variants in hematopoietic stem cells and/or clonal selection pressure exerted by the DNA-damaging agents, and immune evasion on top of any inherited genetic susceptibility. (sahmri.org.au)
Mutations that occur2
  • Somatic mutations are mutations that occur after a person is conceived and in cells other than sperm or egg cells, meaning they cannot be passed on to offspring. (spaceref.com)
  • Somatic mutations that occur in the hematopoietic stem cells can often be leukemogenic and lead to clonal expansion of the mutated stem cells, which is known as clonal hematopoiesis. (news-medical.net)
Precursors2
  • The analysis revealed that hematopoietic commitment capacity (PSCs to hematopoietic precursors) is correlated with the expression level of the IGF2 gene independent of the iPSC origins. (nih.gov)
  • During differentiation the expression of stem cell specific genes and markers are often lost and cells acquire gene expression profiles of somatic cells or their precursors. (justia.com)
Promote clonal expansion1
  • Hematopoietic stem cells (HSCs) can acquire somatic mutations that promote clonal expansion, an age-related process detectable in the blood normal individuals. (harvard.edu)
Lead to clonal expansion1
  • As people age, they can acquire somatic mutations that lead to clonal expansion within their population of regenerating hematopoietic stem cells, which in turn can lead to hematological cancer and coronary heart disease. (genomeweb.com)
Mutant hematopoietic1
  • The mutant hematopoietic stem-cell exhibit a survival advantage over normal cells and tend to expand leading to hemolysis. (aacc.org)
Genes13
  • The proteins produced from both genes are involved in a multistep process that connects particular proteins to the surface of cells. (medlineplus.gov)
  • However, for the condition to occur, they need to also acquire a somatic variant that deletes the other copy of the PIGT gene and other genes around it. (medlineplus.gov)
  • The inflammatory effect of clonal hematopoiesis driver mutations has also been observed at the single-cell level in the overexpression of inflammatory genes. (news-medical.net)
  • Monocytes, which had the most differentially regulated genes, were subclustered as classical, non-classical, and intermediate monocytes, and the enrichment of the DNMT3A mutant cells was examined across these subclusters. (news-medical.net)
  • The researchers also investigated how the DNMT3A mutations influenced subsets of T cells, despite the fact that T cells exhibited a substantially lower number of upregulated genes. (news-medical.net)
  • The upregulation of genes associated with phagocytosis and inflammation was higher in the monocytes, and increased effector function and activation signatures were prominent in the T cells and NK cells. (news-medical.net)
  • Induced pluripotent stem cells (iPSC) express genes associated with pluripotency, have the capacity for infinite expansion, and can differentiate into cells from all three germ layers. (biomedcentral.com)
  • Generally, when a stem cell culture is induced to differentiate, the differentiated population is analysed for particular cell types by expression of genes, markers or phenotypic analysis. (justia.com)
  • Methods of inducing differentiation in stem cells and muscle cells produced therefrom may be used for the study of cellular and molecular biology of tissue development, for the discovery of genes and proteins such as differentiation factors that play a role in tissue development and regeneration. (justia.com)
  • The frequency of somatic mutations in WTC-exposed first responders showed an age-related increase and predominantly affected DNMT3A , TET2 and other CH-associated genes. (nature.com)
  • Found within Wharton's jelly - which is easily harvested from what would otherwise be post-natal medical waste - are several distinct stem cell genes. (articlecity.com)
  • Myelodysplastic syndromes are a group of clonal hematopoietic stem cell disorders unified by the presence of distinct mutations of hematopoietic stem cells, most frequently in genes involved in RNA splicing. (msdmanuals.com)
  • This includes the analysis of genes in germline stem cell proliferation and differentiation. (ncl.ac.uk)
HSCs6
  • Long-term hematopoietic stem cells (LT-HSCs) maintain hematopoietic output throughout an animal's lifespan. (biorxiv.org)
  • Here, we show that young and aged LT-HSCs respond differently to inflammatory stress, such that aged LT-HSCs produce a cell-intrinsic, myeloid-biased expression program. (biorxiv.org)
  • Using single-cell RNA-seq, we identify a myeloid-biased subset within the LT-HSC population (mLT-HSCs) that is much more common amongst aged LT-HSCs and is uniquely primed to respond to acute inflammatory challenge. (biorxiv.org)
  • Aged LT-HSCs demonstrate a cell-intrinsic myeloid bias during inflammatory challenge. (biorxiv.org)
  • FLT3 ITD triggers the proliferation of the quiescent hematopoietic stem cell (HSC) pool but fails to directly transform HSCs. (biomedcentral.com)
  • Human hematopoietic stem cells (HSCs), like their counterparts in mice, comprise a functionally and molecularly heterogeneous population of cells throughout life that collectively maintain required outputs of mature blood cells under homeostatic conditions. (ashpublications.org)
Acute myeloid6
  • CSCs were first identified in hematological cancer such as acute myeloid leukemia in the late '90s when scientists isolated a subpopulation of leukemia cells that expressed the surface marker CD34 but not CD38. (atlasantibodies.com)
  • Somatic mutations in acute myeloid leukemia are acquired sequentially and hierarchically. (ox.ac.uk)
  • Therapy-resistant leukemia stem and progenitor cells (LSC) are a main cause of acute myeloid leukemia (AML) relapse. (bvsalud.org)
  • T cells are important for the control of acute myeloid leukemia (AML), a common and often deadly malignancy. (bvsalud.org)
  • 5 Hematopoietic disruptions in the myeloid lineage can lead to 3 major disease categories: acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), and myelodysplastic syndrome (MDS). (oncomine.com)
  • A heterogenous group of myeloid disorders characterized by somatically mutated hematopoietic stem cells,the presence of variable peripheral cytopenias, and a broad risk of progression to acute myeloid leukemia (AML). (standardofcare.com)
Embryonic stem6
  • In particular, the invention relates to methods of inducing differentiation of embryonic stem cells into muscle cells or vascular endothelial cells. (justia.com)
  • However, the molecular pathways that lead to specification and terminal differentiation of specific cell types, such as myocytes, from embryonic stem cells during development are not entirely clear. (justia.com)
  • Embryonic stem cells, which must be extracted from embryos three to five days old (known as blastocysts, which contain only about 150 cells at this point of development). (articlecity.com)
  • Adult stem cells, which are present in small amounts in adult tissue but less adaptable than embryonic stem cells, making their use in medical treatments more challenging. (articlecity.com)
  • They have many of the positive characteristics of embryonic stem cells while sourcing material is far less challenging, since postpartum tissue can be used. (articlecity.com)
  • Embryonic stem cells are derived from the inner cell mass of a blastocyst, which is an accumulation of primordial cells (4-5 days after fertilization). (bvsalud.org)
Genetics3
  • A comprehensive new study from deCODE genetics, a subsidiary of Amgen, published today in Nature Genetics, provides insights into the epidemiology and somatic and germline genetics of clonal hematopoiesis. (decode.com)
  • The clone has a advantage provided by the somatic genetics change with driver mutations. (standardofcare.com)
  • There is a kind of zeitgeist that findings in genetics, namely somatic mutations, are reflexively viewed as being causative for carcinogenesis, although some 80% of all cancers are presently termed "sporadic" (i.e., with no proven cause). (4open-sciences.org)
DNMT3A11
  • Bone marrow transplants involving cells heterozygous for DNMT3A and TET2 have also resulted in increased infiltration of the heart with T cells and macrophages. (news-medical.net)
  • Single-cell ribonucleic acid sequencing (scRNA-seq) can be used to identify the cells with clonal hematopoiesis driver mutations in the DNMT3A gene to understand their role in heart failure. (news-medical.net)
  • In the present study, the researchers used Oxford Nanopore long-read sequencing to conduct scRNA-seq to detect DNMT3A mutant cells among circulating immune cells from patients with heart failure. (news-medical.net)
  • A method called MutDetect-seq was developed to identify single cells with DNMT3A mutations. (news-medical.net)
  • The MutDetect-seq method was applied to samples of circulating immune cells from five heart failure patients known to have DNMT3A mutations. (news-medical.net)
  • An adapted bioinformatics pipeline was then used to identify the cells with specific coding sequence mutations in the DNMT3A gene. (news-medical.net)
  • Additionally, naïve CD4 + T cells were also subjected to DNMT3A silencing to understand the direct effects of DNMT3A mutations on T-cell function. (news-medical.net)
  • Similar DNMT3A silencing was also performed in natural killer (NK) cell lines to determine the role of the DNMT3A gene in NK cells. (news-medical.net)
  • The findings reported that altered gene expression profiles were identified in monocytes, NK cells, and CD4 + T cells containing DNMT3A mutations. (news-medical.net)
  • The multipotent nature of DNMT3A CHIP mutations, which had been reported in various previous studies, was confirmed in the present study, where cells with DNMT3A mutations were retrieved from all major immune cell populations. (news-medical.net)
  • DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. (haematologica.org)
Germline genetic1
  • 3. Identification of somatic and germline genetic abnormalities associated with the development of myeloid malignancies. (ox.ac.uk)
Malignant6
  • The FDA's 2009 "Guidance on Prophylactic DNA Vaccines: Analysis and Recommendations" states that concerns about plasmid DNA potentially integrating into the genome of the vaccine recipient and increasing the likelihood of issues like "malignant transformation, genomic instability, or cell growth dysregulation" were raised when DNA vaccines were initially introduced for clinical use. (zerohedge.com)
  • Our overarching aim is to improve the management of myeloproliferative neoplasms and related conditions through better monitoring and therapeutic targeting of malignant stem cell populations. (ox.ac.uk)
  • Our overarching aim is to better characterise the cellular and molecular biology of these key populations of cells in order to understand how malignant stem cell populations might be more effectively targeted and eradicated. (ox.ac.uk)
  • We have developed new methods to study the molecular signatures of normal and malignant stem cell populations at the single-cell level. (ox.ac.uk)
  • This is crucial in order to unravel the intratumoural heterogeneity within any phenotypically defined malignant stem cell population. (ox.ac.uk)
  • There is clonal proliferation of malignant hematopoietic stem cells, dysregulated cellular differentiation, and compromised tissue function. (standardofcare.com)
Self-renewal9
  • They further traced that locus to a likely causal variant that affects a TET2 enhancer to lead to an increase in the self-renewal of hematopoietic stem cells. (genomeweb.com)
  • In a series of assays, they found that individuals with this variant had decreased TET2 expression and that the reduction of TET2 activity was linked to increased self-renewal and proliferation of hematopoietic stem cells. (genomeweb.com)
  • Stem cells can produce more stem cells (self-renewal) and also differentiate and proliferate, giving rise to red blood cells (erythrocytes), white blood cells (leukocytes), and platelets. (rarediseases.org)
  • Cell cycle analysis revealed a loss of quiescence in HSC co-expressing Aml1-ETO and K-RasG12D, accompanied by an enrichment in E2F and Myc target gene expression and depletion of HSC self-renewal-associated gene expression. (ox.ac.uk)
  • In both species, an early developmental change in the HSC population involves a postnatal switch from a state in which most of these cells exist in a rapidly cycling state and maintain a high self-renewal potential to a state in which the majority of cells are in a quiescent state with an overall reduced self-renewal potential. (ashpublications.org)
  • They are able to differentiate into any cell of an organism and have the ability of self-renewal. (articlecity.com)
  • Stem cells are defined by their capacity for self-renewal and multilineage differentiation, making them uniquely situated to treat a broad spectrum of human diseases. (articlecity.com)
  • A stem cell is an undifferentiated unit with powerful self-renewal properties that is capable of organizing other cell types in the body. (bvsalud.org)
  • Stem cells are defined as undifferentiated cells that have precursor properties, are capable of forming many different cell types and have the property of unlimited self-renewal 5 . (bvsalud.org)
Proliferation and differentiation1
  • Scaffolds play an important role in tissue engineering as a substrate that can mimic the native extracellular matrix and the properties of scaffolds have been shown to affect the cell behavior such as the cell attachment, proliferation and differentiation. (wjgnet.com)
Transplant10
  • Cells for HSCT may be obtained from the patient himself or herself (autologous transplant) or from another person, such as a sibling or unrelated donor (allogeneic transplant) or an identical twin (syngeneic transplant). (medscape.com)
  • In 2022 the National Cancer Institute announced a three-year clinical trial to evaluate stem cell transplant as a possible treatment for patients with VEXAS. (wikipedia.org)
  • The more aggressive forms of hematopoietic and lymphoid tissue diseases require treatment with chemotherapy, radiotherapy, immunotherapy and, in some cases, a bone marrow transplant. (atlasantibodies.com)
  • An Autologous Stem Cell Transplant (ASCT) is a component of the FDA standard-of-care therapy plan for all newly diagnosed myeloma patients. (peoplebeatingcancer.org)
  • Hematopoietic cell transplant aka the procedure referred to as a stem cell transplant, either allogeneic or autologous, is high-dose therapy, is aggressive and therefore hard on the myeloma patient's heart. (peoplebeatingcancer.org)
  • Autologous stem cell transplant (ASCT) refers to a medical procedure in which a person's own stem cells are collected and then reintroduced into their body after high-dose chemotherapy or radiation therapy. (peoplebeatingcancer.org)
  • Characteristics and risk of chronic graft-versus-host disease of liver in allogeneic hematopoietic stem cell transplant recipients. (cdc.gov)
  • Clinical outcomes of HLA-DPB1 mismatches in 10/10 HLA-matched unrelated donor-recipient pairs undergoing allogeneic stem cell transplant. (cdc.gov)
  • Transplant Cell Ther 2021. (harvard.edu)
  • Defibrotide: Real World Management of Veno-Occlusive Disease/ Sinusoidal Obstructive Syndrome after Stem Cell Transplant. (harvard.edu)
Donor2
  • The National Marrow Donor Program (NMDP), founded in 1986, and the World Marrow Donor Association (WMDA), founded in 1988, were established to (1) locate and secure appropriate unrelated-donor HSCT sources for patients by promoting volunteer donation of bone marrow and peripheral blood stem cells in the community and (2) promote ethical practices of sharing stem cell sources by need, rather than by geographic location of the donor. (medscape.com)
  • Initial experiments revealed that advancing donor age was accompanied by a significant and progressively delayed proliferative response but not the altered mature cell outputs seen in normal older individuals. (ashpublications.org)
TET22
  • This variant predisposes individuals to developing CHIP driven by a number of somatic mutations, suggesting the variant doesn't specifically predispose individuals to TET2-specific CHIP. (genomeweb.com)
  • This, the researchers wrote, shows that "at this locus, both germline noncoding and somatic coding variation converge to affect TET2 and influence the development of CHIP. (genomeweb.com)
Play a pivotal role1
  • 1,2 This shift is due in part to advances in NGS technology, which have propelled the discovery of somatic mutations that play a pivotal role in hematological disorders and the associated development of targeted therapies.2 These newly identified genetic alterations and molecular pathways provide valuable clinical insights across the continuum of care. (oncomine.com)
Leukemia8
  • Individuals with PNH are at increased risk of developing cancer in blood-forming cells (leukemia). (medlineplus.gov)
  • Somatic TP53 mutations have been observed in patients with SDS who develop MDS 13 , raising the possibility that next-generation sequencing could be integrated into surveillance for somatic clones with enhanced leukemia potential. (nature.com)
  • Acute (AML) and chronic (CML) myeloid leukemia are cancers of the myeloid line of blood cells, characterized by the rapid growth of abnormal cells that build up in the bone marrow and blood and interfere with normal blood cell production. (atlasantibodies.com)
  • SIGNIFICANCE: The elimination of therapy-resistant leukemia stem and progenitor cells (LSC) remains a major challenge in the treatment of AML. (bvsalud.org)
  • Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. (bvsalud.org)
  • Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. (ox.ac.uk)
  • The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. (edu.au)
  • Leukemia is characterized by the abnormal and uncontrolled expansion of malfunctioning blood cells that crowd out normal cells. (lu.se)
Populations3
  • We are also applying this approach to analyse patients receiving novel targeted therapies in order to better understand mechanisms of resistance to molecularly targeted therapy in stem cell populations and pathways of transformation to more aggressive forms of disease. (ox.ac.uk)
  • 4. Characterisation of cell-extrinsic regulators of haematopoietic stem/progenitor cells, including bone marrow niche populations, and how they are disrupted during the development of myeloproliferative neoplasms and related conditions. (ox.ac.uk)
  • Bone marrow appears to contain three stem cell populations: hematopoietic stem cells, stromal stem cells and endothelial precursor cells. (bvsalud.org)
Abnormal4
Lineage4
  • GS-2 iPSCs showed the capacity to differentiate into cells of the hematopoietic lineage. (biomedcentral.com)
  • Whilst differentiation of some lineage specific stem cells can be induced with a degree of certainty, a differentiation outcome of a population of pluripotent stem cells is less predictable. (justia.com)
  • Distinguishing mutational status at the single-cell level offers precision in diagnosis and informs treatment options, and clonal lineage reconstruction provides a comprehensive picture of the disease progression. (genomeweb.com)
  • Criteria for diagnosis of MDS consist of anemia, thrombocytopenia, or neutropenia that persist for six months or longer, dysplasia greater than 10% in at least one bone marrow cell lineage, and MDS associated clonal cytogenetic abnormalities or molecular markers. (standardofcare.com)
Transcriptional3
  • One sentence summary Murine hematopoietic stem cells display transcriptional heterogeneity that is quantitatively altered with age and leads to the age-dependent myeloid bias evident after inflammatory challenge. (biorxiv.org)
  • Single-cell RNA-seq of primary AML samples and CD4 + T cells before and after their interaction uncovered transcriptional programs that correlate with AML sensitivity or resistance to CD4 + T cell killing. (bvsalud.org)
  • We show that AML transcriptional programs correlate with susceptibility to T cell killing. (bvsalud.org)
Gene expression1
  • This method combines the long-read sequences obtained using the Oxford Nanopore technology with short-read sequences from single-cell gene expression profiles. (news-medical.net)
Regulator2
  • Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease. (edu.au)
  • First, we looked at LIN28B, a gene recognized as the master regulator of fetal blood cell formation. (lu.se)
Blood cells31
  • Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired (not inherited) disorder that leads to the premature death and impaired production of blood cells. (medlineplus.gov)
  • During these episodes, red blood cells are broken down earlier than they should be (hemolysis). (medlineplus.gov)
  • People with PNH may also be prone to infections because of a shortage of white blood cells (leukopenia). (medlineplus.gov)
  • and give rise to the various types of blood cells. (medlineplus.gov)
  • The mutations identified in this study were characterized by the overrepresentation of blood cells derived from a single clone, a process called clonal hematopoiesis (CH). Such mutations are frequently caused by environmental factors, such as exposure to ultraviolet radiation or certain chemicals, and may be a result of cancer chemo- or radiotherapy. (spaceref.com)
  • The researchers collected whole blood samples from the astronauts 10 days before their flight and on the day of landing, and white blood cells only three days after landing. (spaceref.com)
  • Clinical manifestations of PNH occur when a HSC clone carrying somatic PIGA mutations acquires a growth advantage and differentiates, generating mature blood cells that are deficient of GPI-anchored proteins. (medscape.com)
  • CD59 also called membrane inhibitor of reactive lysis (MIRL) forms defensive shield for red blood cells to inhibit the assembly of the membrane attack complex. (aacc.org)
  • In PNH patients these two complement regulatory proteins are absent or partially expressed on red blood cells. (aacc.org)
  • This deficiency is seen in white blood cells and red blood cells. (aacc.org)
  • As a result, PNH is characterized by continuous destruction of PNH red blood cells due to vulnerability to complement mediated lysis. (aacc.org)
  • This figure illustrates the defect in PNH red blood cells. (aacc.org)
  • In normal red blood cells, the small blue arrows attached to the red blood cells surface represent the GPI-anchor needed for the expression of CD59 complement regulatory protein. (aacc.org)
  • GPI-anchor is missing in PNH red blood cells and as a result CD59 is not expressed. (aacc.org)
  • Normal red blood cells can resist the effect of complement activation by the expression of CD59. (aacc.org)
  • PNH red blood cells clone lacks CD59 will undergo hemolysis and release of free hemoglobin in plasma. (aacc.org)
  • As we mentioned, hemolysis is due to complement activation of vulnerable red blood cells. (aacc.org)
  • Acquired aplastic anemia is a rare, serious blood disorder, due to failure of the bone marrow failure to produce blood cells. (rarediseases.org)
  • In acquired aplastic anemia, an almost complete absence of hematopoietic stem cells results in low levels of red and white blood cells and platelets (pancytopenia). (rarediseases.org)
  • The symptoms of acquired aplastic anemia occur as a consequence of the bone marrow failing to produce enough blood cells. (rarediseases.org)
  • Red and white blood cells and platelets are formed in the bone marrow. (rarediseases.org)
  • Red blood cells deliver oxygen to the body's organs, white blood cells help in fighting infections, and platelets form clots to stop bleeding. (rarediseases.org)
  • A low level of circulating red blood cells is called anemia. (rarediseases.org)
  • A low level of white blood cells is known as leukopenia. (rarediseases.org)
  • 10,14 The eventual accumulation of immature white blood cells (myeloblasts or blasts) in the blood and bone marrow impairs other blood cell development and leads to a shortage of red blood cells (anemia) and platelets. (oncomine.com)
  • The overproduction of red blood cells characterizes polycythemia vera (PV), 1 of the 3 commonly classical Philadelphia chromosome-negative, or BCR-ABL, myeloproliferative neoplasms. (oncomine.com)
  • Anemia is accompanied by a reduced number of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. (lecturio.com)
  • Subtypes are classified by the size of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. (lecturio.com)
  • This classification was abandoned because of the observation that surface proteins were missing not only in the RBC membrane but also in all blood cells, including the platelet and white cells. (medscape.com)
  • 35 It is true that I am excluding here as elsewhere red blood cells which have no nucleus once released into the blood, and sperm or eggs with only 1,500,000,000 bases in them. (globalchange.com)
  • PV is a myeloproliferative neoplasm (MPN) of the bone marrow characterized by an overproduction of erythrocytes and often other blood cells. (cdc.gov)
Pathways4
  • To understand the molecular pathogenesis of MN in patients with SDS, we characterized the presence and dynamics of somatic mutations in serial, clinically annotated samples collected prospectively from patients enrolled in the North American SDS Registry and studied the functional consequences of recurrently mutated pathways. (nature.com)
  • The mutant monocytes and T cells also showed increased paracrine signaling pathways as compared to wild-type monocytes and T cells, respectively. (news-medical.net)
  • We also molecularly defined the development of Sertoli, Leydig and peritubular myoid cells during the perinatal period, allowing us to identify candidate signaling pathways acting between somatic and germ cells in a stage-specific manner during the perinatal period. (biologists.com)
  • Trowbridge, J. J. & Starczynowski, D. T. Innate immune pathways and inflammation in hematopoietic aging, clonal hematopoiesis, and MDS. (nature.com)
PIGA3
  • PNH occurs when a somatic variant of the PIGA gene or PIGT gene occurs in a blood-forming cell called a hematopoietic stem cell. (medlineplus.gov)
  • PNH is caused by somatic mutations in PIGA (which encodes phosphatidylinositol N-acetylglucosaminyltransferase subunit A) in one or more HSC clones. (medscape.com)
  • The product of the PIGA gene is required for the synthesis of anchor protein known as GPI- anchor that ties other proteins to the cell surface. (aacc.org)
Patients11
  • The name VEXAS is an acronym deriving from the core features of disease: V: Vacuoles are often identified in the bone marrow stem cells of patients presenting with VEXAS. (wikipedia.org)
  • A: Patients with VEXAS present with a wide array of Autoinflammatory conditions S: The mutations which cause VEXAS are somatic: they are acquired throughout life, not inherited, and are not passed on to offspring. (wikipedia.org)
  • To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. (nature.com)
  • Complete normalization of hemoglobin (complete and major hematological response), is seen in no more than one third of patients, while the remaining continue to experience some degree of anemia (good and partial hematological responses), in some cases requiring regular red blood cell transfusions (minor hematological response). (frontiersin.org)
  • Functional relevance of shared AML/LSC antigens is illustrated by presence of their cognizant memory T cells in patients. (bvsalud.org)
  • Together, these antigens shared among AML and LSCs represent prime targets for T cell-based therapies with potential of eliminating residual LSCs in patients with AML. (bvsalud.org)
  • This study identifies and functionally validates LSC-associated HLA class I and HLA class II-presented antigens, paving the way to the development of LSC-directed T cell-based immunotherapeutic approaches for patients with AML. (bvsalud.org)
  • Clonal hematopoiesis in patients receiving chimeric antigen receptor T-cell therapy. (harvard.edu)
  • Patients with the greater number of somatic mutations have inferior overall survival. (standardofcare.com)
  • The key to these cells' utility is their ability to differentiate into many different cell types depending on the stimulus received and they have been used in treatments for diseases such as cancer and neural degeneration, in rehabilitation of tetraplegic and paraplegic patients and even in dentistry 1 . (bvsalud.org)
  • 7. A CD19+ cell proportion of = 1 % of the total lymphocyte count in patients exposed to other anti-B-cell therapies more than 6 months before signing the informed consent form. (who.int)
20161
  • Physiologic aging in both humans and mice leads to permanent changes in LT-HSC function, such as myeloid-biased hematopoietic output ( Akunuru and Geiger, 2016 ). (biorxiv.org)
Therapies2
  • Regenerative and reparative properties of somatic cell-based therapies hold tremendous promise for repairing injured tissue, preventing and reversing damage to organs, and restoring balance to compromised immune systems. (nih.gov)
  • The old model of tMN development in which mutations accumulate in hematopoietic stem and progenitor cells (HSPCs) induced directly by cytotoxic therapies has been challenged by newer data. (harvard.edu)
Peripheral2
  • The RAB27A protein is responsible for the peripheral distribution of melanosomes in melanocytes and exocytosis of cytotoxic granules in the cytosol of cytotoxic T cells (CTL) and natural killer (NK) cells. (biomedcentral.com)
  • Clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral cytopenias. (standardofcare.com)
Microenvironment1
  • Cancer stem cells (CSCs) are generated by a combination of DNA mutations, epigenetic events, and tissue microenvironment factors from normal stem cells or precursor/progenitor cells, to which they are closely related and share many of the behaviors and features 1 . (atlasantibodies.com)
Outcome3
  • Low T Cell Numbers Resembling T-B+ SCID in a Patient with Wiskott-Aldrich Syndrome and the Outcome of Two Hematopoietic Stem Cell Transplantations. (medscape.com)
  • Antigen-specific T-cell recognition and HLA class II immunopeptidome diversity correlated with clinical outcome. (bvsalud.org)
  • Placing the cells under conditions which induce specific cell types has been one form of an attempt to regulate the differentiation outcome. (justia.com)
Chronic1
  • This Special Issue contains separate papers discussing undervalued ubiquitous proteins, chronic inflammation, eicosanoids, microbiome and morbid obesity, PCN, cell transition, followed by altered signaling induced by Metformin, NF-κB signaling and crosstalk during carcinogenesis, and a brief synopsis. (4open-sciences.org)
Differentiate1
Tumors4
  • One crucial ability of the CSCs is to form tumors already at low cell numbers. (atlasantibodies.com)
  • On the other hand, in brain tumors, such as glioma and glioblastoma, CSCs have instead been identified using cell surface markers, including SSEA-1 20 , EGFR 21 , and CD44 22 . (atlasantibodies.com)
  • Resolving the Pathogenesis of Anaplastic Wilms Tumors through Spatial Mapping of Cancer Cell Evolution. (lu.se)
  • 6. Malignancies, including a history thereof, with the exception of cured basal cell carcinoma, cervical cancer in situ, as well as cured solid tumors with a remission of more than 5 years. (who.int)
Differentiation capacity2
  • Differentiation capacity into cells from all three germ layers was confirmed using the teratoma assay. (biomedcentral.com)
  • These data demonstrated that variations in the hematopoietic differentiation capacity of iPSCs are not attributable to somatic memories of their origins. (nih.gov)
Stromal2
  • MyeloCult™ media have been developed for the long-term culture of hematopoietic progenitor cells in association with adherent stromal cells. (stemcell.com)
  • Stromal cell feeder layers (e.g. (stemcell.com)