• Here, we explored GATA-mediated transcriptional regulation through the integrative analysis of gene expression, chromatin modifications, and GATA factors' binding in human multipotent hematopoietic stem/progenitor cells, early erythroid progenitors, and late precursors. (unisr.it)
  • GATA factors mediate transcriptional changes through a stage-specific interplay with regulatory elements: GATA1 binds different sets of regulatory elements in erythroid progenitors and precursors and controls the transcription of distinct genes during commitment and differentiation. (unisr.it)
  • Finally, we demonstrated that GATA1 binding to a stage-specific super-enhancer sustains the expression of the KIT receptor in human erythroid progenitors. (unisr.it)
  • Although previous protocols have generated clonogenic progenitors and various differentiated hematopoietic cells, there is no confirmation of their definitive identity or functional HSC properties. (researchsquare.com)
  • Many protocols have been described that achieve the generation of clonogenic progenitors and various differentiated hematopoietic cells. (researchsquare.com)
  • Prior to the generation of HSCs, large quantities of myelo-erythroid progenitors are generated in the yolk sac. (researchsquare.com)
  • It has been proposed that hematopoietic differentiation from pluripotent stem cells is biased toward the generation of the yolk sac like differentiation-primed progenitors. (researchsquare.com)
  • We show that treatment of EB-derived CD34+ cells with a pulse of retinoic acid receptor alpha agonist (AM580) during the first days of stroma co-culture promotes the definitive HSC fate by inducing the expression of developmental regulators of definitive HSC genetic program, while suppressing genes associated with differentiation primed progenitors. (researchsquare.com)
  • Polycythemia is categorized as primary or secondary due to intrinsic or extrinsic changes, respectively, to erythroid progenitors and RBCs. (medscape.com)
  • Red cell development is initially regulated by stem cell factor (SCF), which commits hematopoietic stem cells to develop into erythroid progenitors. (medscape.com)
  • In parallel, we used a version of the SMART-Seq2 protocol to obtain deep sequencing data (4-7,000 genes/cell) from 400 mitotic progenitors. (authorea.com)
  • Finally, we added data produced using the 10X genomics system for 7,000 postmitotic progenitors with significantly increased sequencing depth (1,500-11,000 UMI/cell, 1,000-4,000 genes/cell), and observed identical branching patterns as in our original Drop-seq dataset. (authorea.com)
  • Cre ;Ai9 line that uniformly marks interneuron progenitors, We therefore collected a set of 15,522 single cells across a developmental timecourse (E13.5, E18, P10), obtaining 3,432 additional P56 cells from a public resource hosted by the Allen Brain Atlas. (authorea.com)
  • To produce RBCs, HSCs differentiate into megakaryocyte-erythroid progenitors and then burst forming unit-erythroid (BFU-E) and colony-forming unit-erythroid (CFU-E). Upon erythropoietin (EPO) stimulation, CFU-E further develops into various erythroid precursors (proerythroblasts, basophilic erythroblasts, polychromatic erythroblasts, and orthochromatic erythroblasts). (biomedcentral.com)
  • 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)
  • Moreover, in human studies, JAK2V617F has been identified in the stem cell-enriched CD34 + CD38 − CD90 + Lin − compartment, common myeloid progenitors, granulocyte-monocyte precursors, and megakaryocyte-erythroid precursors as well as natural killer cells, B cells, and T cells in some patients, confirming its origin in an early hematopoietic progenitor. (oncohemakey.com)
  • Osteoblasts are mononucleated mesenchymal stem cells that form bone matrix, whereas osteoclasts are bone-resorbing multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage [ 3 , 4 , 5 ]. (biomedcentral.com)
  • Here, by manipulating RUNX2 expression with either knockdown or overexpression in human haematopoietic stem cell-based NK cell differentiation cultures, combined with transcriptomic and ChIP-sequencing analyses, we established that RUNX2 drives the generation of NK cells, possibly through induction of IL-2Rß expression in NK progenitor cells. (bvsalud.org)
  • Human CD34 + hematopoietic stem and progenitor cells purified from umbilical cord or adult peripheral blood were cultured in a two-phase liquid culture system in a serum-free medium for 21 days. (haematologica.org)
  • This protocol generates cells that resemble human foetal liver hematopoietic stem/progenitor cells (HSPC) by immunophenotype (CD34+CD38loCD90+CD45+GPI80+/-) and molecular profile. (researchsquare.com)
  • CRISPR/Cas9-mediated TPM1 knockout in human induced pluripotent stem cells (iPSCs) enhanced hematopoietic progenitor development, increasing total megakaryocyte and erythroid cell yields. (biomedcentral.com)
  • To validate this putative candidate gene and to explore its function, we used CRISPR/Cas9 genome editing to discover that cultured TPM1 -deficient induced pluripotent stem cells enhanced hematopoietic progenitor cell formation. (biomedcentral.com)
  • MyeloCult™ media have been developed for the long-term culture of hematopoietic progenitor cells in association with adherent stromal cells. (stemcell.com)
  • Although hematopoietic stem and progenitor cells (HSPCs) enable autologous treatment of blood disorders, de novo generation of hematopoietic cells from pluripotent stem cells still compromises the unlimited high yield and rich hematopoiesis engraftment potential [ 2 ]. (biomedcentral.com)
  • Early fate decisions in hematopoietic stem and progenitor cells. (lu.se)
  • Hematopoiesis occurs in the bone marrow, producing a complete spectrum of blood cells to maintain homeostasis. (biomedcentral.com)
  • GATA-2 has a broad role in hematopoietic development, as demonstrated by impaired hematopoiesis in Gata2 knock-out mice resulting in lethality during midgestation [8] , [9] . (prolekarniky.cz)
  • Decades of efforts have attempted to differentiate the pluripotent stem cells (PSCs) into truly functional hematopoietic stem cells (HSCs), yet the problems of low differentiation efficiency in vitro and poor hematopoiesis reconstitution in vivo still exist, mainly attributing to the lack of solid, reproduced, or pursued differentiation system. (biomedcentral.com)
  • The Snail family and hematopoiesis At this time there is usually no data elucidating the role of within the LY2603618 (IC-83) hematopoietic system. (bioinf.org)
  • This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization. (biomedcentral.com)
  • This mechanism also applies to hematopoietic cells transformed by other HOX genes, including CDX2, which is highly expressed in a majority of acute myeloid leukemias, thus providing a molecular approach based on GSK-3 inhibitory strategies to target HOX-associated transcription in a broad spectrum of leukemias. (stanford.edu)
  • [ 3 ] The 2016 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia continued to recognize pure erythroid leukemia but eliminated the erythroid/myeloid type of acute erythroleukemia. (medscape.com)
  • Cases previously classified as erythroid/myeloid subtype, based on the 2008 WHO classification, are currently categorized either as myelodysplastic syndrome with excess blasts or acute myeloid leukemia, not otherwise specified. (medscape.com)
  • In vivo work showed that the outcomes of disease (erythroid, myeloid, or both) depend on the driving oncogene and the hematopoietic target cell in which it is aberrantly expressed. (medscape.com)
  • Inhibition of HOX/PBX dimer formation leads to necroptosis in acute myeloid leukemia cells ONCOTARGET. (nottingham.ac.uk)
  • The chronic myeloproliferative neoplasms (MPNs) are clonal disorders characterized by overproduction of mature myeloid cells. (oncohemakey.com)
  • The MPNs comprise a set of clonal HSC disorders, characterized by the overproduction of 1 or more mature myeloid cell types. (oncohemakey.com)
  • Of note LAMA-84 cells were originally derived from a chronic myeloid leukemia (CML) patient undergoing blast crisis [22]. (bioinf.org)
  • The mechanism of upregulation becomes relevant when one considers that c-Kit is usually highly expressed on the surface of acute myeloid leukemia (AML) cells [23 24 Unfortunately this study did not conduct any experiments to assess the downstream consequences of induction in LAMA-84 cells. (bioinf.org)
  • MDS was found to be related to genetic mutations or epigenetic modifications, which lead to abnormal autophagy, apoptosis of mature cells, chromosomal abnormalities, and a high level of inflammation in the bone marrow microenvironment ( 4 - 8 ). (frontiersin.org)
  • [ 1 ] Patients usuallly present with nonspecific signs and symptoms from the anemia, thrombocytopenia, and leukopenia resulting from the replacement of bone marrow by leukemic cells (see Presentation ). (medscape.com)
  • While the embryoid body differentiation generates immature haematovascular precursors, co-culture on mouse bone marrow OP9M2 stroma 3 enables subsequent maturation step of the CD34+ haemato-vascular cells to immunophenotypic human HSPCs. (researchsquare.com)
  • Two-color analysis of the expression of CD117 on mouse bone marrow cells. (bdbiosciences.com)
  • A single-cell suspension of BALB/c bone marrow was simultaneously stained with FITC Rat Anti-Mouse CD45R/B220 (Cat. (bdbiosciences.com)
  • In PV, bone marrow panmyelosis is associated with increased numbers of red blood cells and, in some patients, neutrophilia and/or thrombocytosis. (oncohemakey.com)
  • These early studies demonstrated that expression of JAK2V617F in retroviral bone marrow transplantation models caused erythrocytosis, confirming its relevance to human MPNs. (oncohemakey.com)
  • Deficient reticulocyte production, intramedullary death of red blood cells (RBCs), and bone marrow erythroid hyperplasia (and dysplasia) occur. (msdmanuals.com)
  • Bone is a highly dynamic organ that is continuously remodeled by coordinated activities of two cell types, osteoclasts and osteoblasts [ 1 , 2 ]. (biomedcentral.com)
  • PV is a myeloproliferative neoplasm (MPN) of the bone marrow characterized by an overproduction of erythrocytes and often other blood cells. (cdc.gov)
  • Acute myelogenous leukemia (AML) is a malignant disease of the bone marrow in which hematopoietic precursors are arrested in an early stage of development. (medscape.com)
  • The underlying pathophysiology in AML consists of a maturational arrest of bone marrow cells in the earliest stages of development. (medscape.com)
  • Patients with AML present with symptoms resulting from bone marrow failure, symptoms resulting from organ infiltration with leukemic cells, or both. (medscape.com)
  • Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation. (molcells.org)
  • The up-regulation of miR-199b-5p during erythroid differentiation was dependent on the binding of GATA-1 and NF-E2 to its gene locus, which activated its transcription and maintained its high expression level in mature erythroid cells. (molcells.org)
  • We are studying the role that normal chromatin structure plays in gene regulation in hematopoietic cells and how its disruption leads to altered development and cancer. (stanford.edu)
  • Our studies have demonstrated that several of the proteins encoded by cellular oncogenes function in fundamental aspects of gene regulation. (stanford.edu)
  • This widespread expression of CD117 in hematopoietic precursors is consistent with the participation of c-Kit and its ligand in the regulation of several hematopoietic lineages. (bdbiosciences.com)
  • Intrathymic expression of c-Kit and c-Kit ligand suggest that CD117 is also involved in the regulation of some events during the development of T lymphocytes. (bdbiosciences.com)
  • CD31 (platelet endothelial cell adhesion molecule-1, PECAM-1) is an inhibitory coreceptor involved in regulation of T cell and B cell signaling by a dual immunoreceptor tyrosine-based inhibitory motif (ITIM) that upon associated kinases-mediated phosphorylation provide docking sites for protein-tyrosine phosphatases. (thermofisher.com)
  • CD31 is a multifunctional molecule with diverse roles in modulation of integrin-mediated cell adhesion, transendothelial migration, angiogenesis, apoptosis, negative regulation of immunoreceptor signaling, autoimmunity, macrophage phagocytosis, IgE-mediated anaphylaxis and thrombosis. (thermofisher.com)
  • Here, we have analyzed cis element regulation of the critical hematopoietic factor Gata2 , which is expressed in early precursors and repressed as GATA-1 levels rise during terminal differentiation. (prolekarniky.cz)
  • Models of gene regulation have led to an attractive paradigm in which repression occurs in sequential stages of increasing stability [4] . (prolekarniky.cz)
  • Regulation of hematopoietic stem cells in niche signaling]. (elsevierpure.com)
  • NFATs are a family of TFs that are physiologically activated by the calcium-activated serine/threonine phosphatase calcineurin, which dephosphorylates NFAT, thereby leading to their nuclear translocation and target gene regulation [ 5 ]. (biomedcentral.com)
  • Recently, we developed a hematopoietic stem cell-based approach to tackle this issue, in which we can genetically alter nucleated hematopoietic precursor cells and differentiate them ex-vivo to mature erythrocytes that can be infected by P. falciparum. (stanford.edu)
  • We first optimized a serum-free, miniature erythroid differentiation system starting from primary human CD34 cells, the exact type of cells we would ultimately like to target in vivo ( Figure 1 ). (haematologica.org)
  • Here, we describe a two-step differentiation protocol for H1 hESC that combines 2 weeks of embryoid body differentiation in mesoderm inducing conditions followed by OP9M2 stroma co-culture in HSC supportive conditions, which enables the generation of hematopoietic cells that resemble foetal liver HSPCs by immunophenotype (CD34+CD38loCD90+CD45+GPI80+) 2 and molecular profile. (researchsquare.com)
  • In this regard, his lab has identified a novel family of hematopoietic cell surface proteins, called the CD34 family, and shown that these are essential for a number of developmentally important processes. (ubc.ca)
  • Although the utility of these prognostic assessment systems has been confirmed in clinical practice, they do not take gene mutations into account ( 13 ). (frontiersin.org)
  • Multiple gene mutations have been identified and considered as important substrates for the development of MDS, such as RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements. (frontiersin.org)
  • The leukemic cells in erythroleukemia often carry complex karyotypes and mutations in oncogenes known to be associated with AML. (medscape.com)
  • Primary polycythemias are due to factors intrinsic to red cell precursors caused by acquired or inherited mutations. (medscape.com)
  • Mutations in TET2, other epigenetic regulators, and other regulators of cytokine signaling are not specific to the classic myeloproliferative neoplasms (MPNs) but may influence prognosis and play roles in hematopoietic stem cell (HSC) dysregulation and progression to accelerated or blast-phase disease. (oncohemakey.com)
  • Somatic mutations in genes involved in RNA splicing, most frequently SF3B1 (splicing factor 3b subunit 1), commonly occur. (msdmanuals.com)
  • In Section II, Dr. James Griffin reviews the mechanisms that lead to activation of tyrosine kinases by mutations in AML, the consequences of that activation for the cell, and the opportunities for targeted therapy and discusses some examples of developing novel drugs (tyrosine kinase inhibitors) and their effectiveness in AML (FLT3). (ashpublications.org)
  • Germline mutations in the gene AML1 ( RUNX1, CBFA2 ) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML. (medscape.com)
  • For instance, the existence of tissue-specific gene clusters may be related to the efficient activation of gene expression in a particular cell lineage, by genetic and epigenetic mechanisms, or related to the repression of entire chromosomal regions containing genes expressed in a specific cell type, e.g. during the developmental switches leading to different cell lineages [ 25 ]. (biomedcentral.com)
  • Using human K562 erythroleukemia cells capable of differentiating along erythroid and megakaryocytic lineages, we explore the differentiation-related role of heat shock transcription factor 2 (HSF2), which belongs to a family of transcription factors generally known to regulate heat shock gene expression. (abo.fi)
  • Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. (bvsalud.org)
  • and the very uncommon pure erythroid subtype, characterized by expansion of immature erythroid cells only. (medscape.com)
  • Depletion of Runx1 with antisense morpholino oligonucleotides abrogated the development of both blood and vessels, as demonstrated by loss of circulation, incomplete development of vasculature and the accumulation of immature hematopoietic precursors. (biologists.com)
  • To form mature RBCs, the terminal maturation of erythroid cells involves two steps: (1) the condensation and expulsion of the nucleus to form reticulocytes and (2) the organelle clearance and remodeling of the membrane and proteome [ 1 , 7 ]. (biomedcentral.com)
  • The pathophysiological processes that contribute to SMA involve direct and indirect destruction of parasitized and non-parasitized red blood cells (RBCs), inefficient and/or suppression of erythropoiesis, and dyserythropoiesis. (ijbs.com)
  • Overview of Decreased Erythropoiesis Anemia, a decrease in the number of red blood cells (RBCs), hemoglobin (Hb) content, or hematocrit (Hct), can result from decreased RBC production (erythropoiesis), increased RBC destruction. (msdmanuals.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)
  • Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. (molcells.org)
  • We describe a two-step differentiation protocol that starts with differentiation of H1 human embryonic stem cells (hESCs) into embryoid bodies (EBs) in mesoderm-inducing conditions followed by maturation of EB derived CD34+ cells on OP9M2 stroma on HSC supportive conditions. (researchsquare.com)
  • There he worked with Dr. Max D. Cooper (Howard Hughes Medical Institute, National Academy of Sciences) and his research focused on cell surface proteins expressed by preB cells that regulate B cell maturation and homing. (ubc.ca)
  • There his work focused on transcriptional control of hematopoietic stem cell maturation and cell fate. (ubc.ca)
  • The group are currently focused on the pivotal role that HOXA cluster genes play in the demarcation and possible emergence of haematopoietic stem cells (HSCs) and their role in cancer. (nottingham.ac.uk)
  • However, eradication of the leukaemia repopulating cell or stem cell whilst retaining normal HSCs remains a challenge with current experimental therapies. (nottingham.ac.uk)
  • Despite their close molecular correlation to foetal liver HSCs, they are unable to induce the expression of key developmental regulators associated with the HSC fate, such as the HOXA genes. (researchsquare.com)
  • All types of blood cells are derived from hematopoietic stem cells (HSCs). (biomedcentral.com)
  • moreover, they also promote the hematopoietic differentiation of mouse ESCs and favor the development of definitive HSCs from pre-HSCs in the mouse aorta-gonad-mesonephros (AGM) region [ 8 ]. (biomedcentral.com)
  • Transforming acidic coiled-coil-containing protein 3 is a protein that in humans is encoded by the TACC3 gene. (wikipedia.org)
  • Our results reveal a multistep regulatory process of HSF2 gene expression, In K562 cells undergoing hemin-mediated erythroid differentiation, the increase in HSF2 protein levels is preceded by transcriptional induction of the HSF2 gene, accompanied by increased HSF2 mRNA stability. (abo.fi)
  • In contrast, during megakaryocytic differentiation induced by the phorbol ester TPA, expression of HSF2 is rapidly down-regulated, leading to a complete loss of the HSF2 protein. (abo.fi)
  • We demonstrate here that GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, a critical component of the MLL-subordinate program, which in turn facilitates HOX-mediated transcription and transformation. (stanford.edu)
  • We have observed that inactivating EXT1 induces cell enlargement and enhances metabolic switches such as protein secretion. (bvsalud.org)
  • This 130-140 kDa surface protein is expressed by endothelial cells and at low levels on leukocytes and platelets. (thermofisher.com)
  • Among characterized gene candidates, aquaporin 0 (AQP0) expressed as a surface protein in early- and late-stage erythropoiesis precursors and was not expressed on nonerythroid cells. (biomedcentral.com)
  • The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). (bmj.com)
  • This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. (bmj.com)
  • Flow cytometry analysis, RNA-seq, and cell cycle analysis were used to detect the in vitro hematopoietic ability of endothelial protein C receptor (EPCR, CD201) cells generated in our induction system. (biomedcentral.com)
  • The NAMPT protein manifestation in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. (forgetmenotinitiative.org)
  • Silencing of gene also decreased NAMPT protein levels ( (forgetmenotinitiative.org)
  • In vitro hematopoietic systems might be improved by identifying novel factors from human genetic studies. (biomedcentral.com)
  • T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. (bvsalud.org)
  • Gene expression data from 24 experiments for 8 different cell types of the human myelopoietic lineage were used to generate an integrated myelopoiesis dataset of 9,425 genes, each reliably associated to a unique genomic position and chromosomal coordinate. (biomedcentral.com)
  • The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions. (biomedcentral.com)
  • Lineage-specific genes were differently expressed between cells, and correlated with the cell cycle stages with a specific augmentation of erythroid related genes in the G2/M phase. (nih.gov)
  • Most lineage specific TFs were stochastically expressed in the early precursor cells, but a few, such as Klf1, were detected only at very low levels in few precursor cells. (nih.gov)
  • This study reveals effects of cell cycle progression on the expression of lineage specific genes in precursor cells, and suggests that hematopoietic stress changes the balance of renewal and differentiation in these homeostatic cells. (nih.gov)
  • Differentiation of multipotential hematopoietic cells into lineage-committed precursors involves the selection and maintenance of appropriate programs of gene expression, regulated by specific transcription factors. (abo.fi)
  • These results indicate that the determination of HSF2 expression occurs at the early stages of lineage commitment. (abo.fi)
  • Taken together, our data suggest that HSF2 could function as a lineage-restricted transcription factor during differentiation of K562 cells along either the erythroid or the megakaryocytic pathway. (abo.fi)
  • Although Gata2 is normally repressed in late-stage erythroblasts, the −1.8 kb mutation unexpectedly resulted in reactivated Gata2 transcription, blocked differentiation, and an aberrant lineage-specific gene expression pattern. (prolekarniky.cz)
  • runx1 expression in the lateral plate mesoderm co-localizes with the hematopoietic transcription factor scl , and expression of runx1 is markedly reduced in the zebrafish mutants spadetail and cloche . (biologists.com)
  • In astrocytes the OGD enhanced the nuclear translocation of hypoxia-inducible factor 1 (HIF-1), the major transcription factor regulating EPO expression. (jneurosci.org)
  • His laboratory has followed two primary interests: 1) the transcription factor networks that regulate fate determination in various cells that make blood, and 2) the cell surface proteins expressed by hematopoietic stem cells that and allow them to communicate with their microenvironment. (ubc.ca)
  • While the inflammatory transcription factor nuclear factor of activated T-cells 2 ( NFAT2 , NFATC1 ) is overexpressed in AML, it is unknown whether it plays a role in FLT3 ITD -induced HSC transformation. (biomedcentral.com)
  • We generated a triple transgenic mouse model, in which tamoxifen-inducible Cre-recombinase targets expression of a constitutively nuclear transcription factor NFATC1 to FLT3 ITD positive HSC. (biomedcentral.com)
  • 2) We have discovered a group of oncoproteins that are implicated in long-term maintenance of gene expression through their effects on the state of chromatin. (stanford.edu)
  • Transcription factors in these networks occupy specific cis elements at target gene loci where they modulate chromatin remodeling and modification, and thereby transcription. (prolekarniky.cz)
  • MMP-9 plays a direct role in the activation of pro-osteoclastogenic genes by cleaving histone H3N-terminal tail (H3NT) and altering chromatin architecture. (biomedcentral.com)
  • An essential step for understanding gene regulatory pathways at key differentiation time points, therefore, should lie in characterizing the enzymes responsible for reorganizing and potentiating particular chromatin domains. (biomedcentral.com)
  • Not much progress has been made in supporting this idea, but there is some indirect evidence functionally linking chromatin modification to osteoclastogenic gene transcription. (biomedcentral.com)
  • Nonetheless, which factors are mainly responsible for establishing transcriptionally competent chromatin states and exactly how altered chromatin states trigger osteoclastogenic gene transcription remain poorly understood. (biomedcentral.com)
  • Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. (molcells.org)
  • Our research focuses on developmental pathways that regulate hematopoietic cell growth and differentiation and are disrupted in the course of neoplastic transformation, particularly in leukemias and lymphomas. (stanford.edu)
  • Among these prioritized sites were SNPs that regulate TPM1 expression. (biomedcentral.com)
  • Our data establish new functions for G9a-mediated H3K27me1 in MMP-9-dependent H3NT proteolysis and demonstrate how histone modification can be exploited to regulate osteoclastogenic gene expression at the molecular level. (biomedcentral.com)
  • He performed some of the first studies to identify transcription factors that regulate the gene expression and differentiation of eosinophils, which are known to play a major role in allergic and asthmatic responses. (ubc.ca)
  • STAT5 activation seems particularly important for JAK2V617F -induced cytokine independence in vitro and erythrocytosis in vivo and is in itself sufficient to support formation of endogenous erythroid colonies, a cardinal feature of PV. (oncohemakey.com)
  • scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. (nih.gov)
  • Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes. (nih.gov)
  • These factors then initiate multiple signal transduction pathways to turn on downstream genes and activate quiescent osteoclast precursor (OCP) cells to become mature osteoclasts [ 1 , 8 ]. (biomedcentral.com)
  • In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. (molcells.org)
  • 1 The accumulation of free excess α-globin chains in red blood cells and their precursors, as a result of the decreased production of β-globin, is believed to be the main pathophysiological mechanism leading to hemolytic anemia and ineffective erythropoiesis in β-thalassemia. (haematologica.org)
  • After cell sorting, the gene expressions of membrane proteins in early and late erythropoiesis precursors and in nonerythroid cells were characterized using microarray analysis. (biomedcentral.com)
  • In addition, because patients with dyserythropoiesis generally exhibited a reduced population of APQ0 high cells relative to healthy participants, the analysis results also suggested that the levels of APQ0 high cells in early erythropoiesis serve as a novel biomarker that distinguishes normal from dysregulated erythropoiesis. (biomedcentral.com)
  • The expression levels of AQP0 are downregulated in patients with dyserythropoiesis, indicating a critical role of AQP0 in erythropoiesis. (biomedcentral.com)
  • Based on the differential expression levels of cell-surface molecules during erythropoiesis, flow cytometry analysis is a useful tool for analyzing the erythropoiesis process [ 8 ]. (biomedcentral.com)
  • Treatment with a retinoic acid receptor alpha agonist (AM580) during the first six days of stroma co-culture induces the expression of developmental regulators that demarcate the definitive HSC genetic program, including the HOXA genes. (researchsquare.com)
  • scDiffCom is an R package, relying on approximately 5,000 curated ligand-receptor interactions, that performs differential intercellular communication analysis between two conditions from single-cell transcriptomics data. (nature.com)
  • The binding of RANKL to its cognate receptor RANK on pre-osteoclast cell membrane stimulates the expression of key determinants of osteoclast differentiation such as NF-κB, c-Fos, and NFATc1 at the early stage of the process [ 1 , 8 ]. (biomedcentral.com)
  • Built upon scDiffCom, scAgeCom is an atlas of age-related cell-cell communication changes covering 23 mouse tissues from 58 single-cell RNA sequencing datasets from Tabula Muris Senis and the Calico murine aging cell atlas. (nature.com)
  • Usage of the murine IL-3 dependent Baf3 Pro-B cell line exhibited that overexpression of Snai2 was sufficient to confer resistance to apoptosis induced by growth factor withdrawal which was accompanied by exit from the cell cycle [21]. (bioinf.org)
  • In addition to these basic issues concerning leukemia pathogenesis, we are devising new diagnostic procedures for detecting and monitoring leukemia patients based on molecular genetic abnormalities in the malignant cells. (stanford.edu)
  • Kay et al report increased VEGF and bFGF in the supernatant of CLL cells grown in vitro and upregulation of mRNA encoding VEGF and its receptors and bFGF, suggesting that angiogenic factors are important in the biology of the malignant B-cell clone [ 10 ]. (biomedcentral.com)
  • however, it is speculated that it may be involved in cell growth and differentiation. (wikipedia.org)
  • Characterization and validation of the small scale erythroid differentiation system used for small molecule screen. (haematologica.org)
  • In this study, we established an in vitro differentiation system yielding in vivo hematopoietic reconstitution hematopoietic cells from mouse PSCs through a 3D induction system followed by coculture with OP9 stromal cells. (biomedcentral.com)
  • Genetic polymorphisms in Quantitative Trait Loci (QTL) genes such as BCL11A, HBS1L-MYB and KLF1 have been reported to influence fetal hemoglobin (HbF) levels. (mdpi.com)
  • This prospective study was planned to evaluate the role of genetic polymorphisms in QTL genes as determinant of HbF levels in beta thalassemia major patients. (mdpi.com)
  • Identifying causal variants and genes from human genetic studies of hematopoietic traits is important to enumerate basic regulatory mechanisms underlying these traits, and could ultimately augment translational efforts to generate platelets and/or red blood cells in vitro. (biomedcentral.com)
  • As a postdoc in Manoj Duraisingh's lab at Harvard School of Public Health she performed a genetic screen to identify critical host factors for Plasmodium falciparum malaria using red blood cells derived from hematopoietic stem cells. (stanford.edu)
  • Population genetic studies dating back to the mid-20th century first proposed that erythrocytes (red blood cells), the host cell for P. falciparum, have been under natural selection due to malaria. (stanford.edu)
  • Although the notion that malaria has helped shape the human genome is well- accepted, the lack of a nucleus in human erythrocytes has hindered our ability to study genetic interactions between these unusual host cells and P. falciparum parasites. (stanford.edu)
  • X-Linked Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. (msdmanuals.com)
  • The malaria parasite exerted a potent selective signature on the human genome, which is apparent in the genetic polymorphism landscape of genes related to pathogenesis. (biomedcentral.com)
  • The mechanism of this arrest is under study, but in many cases, it involves the activation of abnormal genes through chromosomal translocations and other genetic abnormalities. (medscape.com)
  • Natural killer (NK) cells are innate lymphocytes that eliminate virus-infected and cancer cells by cytotoxicity and cytokine secretion. (bvsalud.org)
  • These cells have the ability to generate progeny associated with definitive haematopoiesis (adult globin expressing erythroid cells and T-lymphocytes) but have limited expansion ability in vitro and cannot engraft in vivo. (researchsquare.com)
  • Multiple myeloma (Millimeter) is a malignancy of W lymphocytes or plasma cells. (forgetmenotinitiative.org)
  • Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where multipotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. (biomedcentral.com)
  • Although transcription factors regulating NK cell development and function have been extensively studied in mice, the role of RUNX2 in these processes has not been investigated, neither in mice nor in human. (bvsalud.org)
  • Importantly, RUNX2 promotes tissue residency in human NK cells. (bvsalud.org)
  • A new histo-blood group system was discovered, based on the identification of Forssman glycolipid antigen on human red blood cells. (ashpublications.org)
  • SummaryThe ability to integrate information across multiple datasets represents an enormous opportunity for the human cell atlas (HCA), yet presents substantial computational challenges. (authorea.com)
  • Here we aim to address a fundamental question for the human cell atlas: how can we integrate a diverse community effort to study a complex human system effectively in order to construct a coherent atlas? (authorea.com)
  • Description: The WM59 monoclonal antibody reacts with human CD31, also known as platelet-endothelial cell adhesion molecule-1 (PECAM-1) and gpIIa. (thermofisher.com)
  • Applications Tested: The WM-59 (WM59) antibody has been tested by flow cytometric analysis of normal human peripheral blood cells. (thermofisher.com)
  • A similar trait-specific gene prioritization strategy could be employed to help streamline functional validation experiments for virtually any human trait. (biomedcentral.com)
  • The manifestation of is usually shown to impact lysosomal size, granule size, and autophagy in human cells [12]. (forgetmenotinitiative.org)
  • He has delineated the function of these molecules in diverse set of biological processes including: 1) gut and kidney formation, 2) vascular permeability, 3) mucosal inflammatory disease, 4) stem cell homing and migration, and 5) epithelial tumor progression. (ubc.ca)
  • Objectives Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells. (bmj.com)
  • The activating effects of the mutation are thought to reflect disruption of the normal autoinhibitory function of the JH2 domain, within which JAK2V617F is found, and have been shown to affect downstream pathways, including STATs (especially STAT5), phosphatidylinositol 3-kinase, and MAP kinase pathways in cell lines and animal models. (oncohemakey.com)
  • Targeted therapies exploit molecular vulnerabilities unique to cancer cells and typically alter cellular signaling pathways to inhibit tumorigenic growth and promote cell death. (biomedcentral.com)
  • Un rôle majeur des prostaglandines dans l'hématopoïèse, ainsi mis en évidence, a pu être étendu à la souris chez qui un traitement par la prostaglandine PGE2 provoque la multiplication des CSH in vivo et in vitro, un résultat qui génerera très probablement des applications cliniques. (hypotheses.org)
  • The in vivo hematopoietic reconstitution potential of c-kit + cells derived from the mouse PSCs was evaluated via m-NSG transplantation assay. (biomedcentral.com)
  • The c-kit + cells from 3D self-assembling peptide induction system followed by the OP9 coculture system possessed apparently superiority in terms of in vivo repopulating activity than that of 3D induction system followed by the 0.1% gelatin culture. (biomedcentral.com)
  • Altogether, our findings lay a foundation for improving the efficiency of hematopoietic differentiation and generating in vivo functional HSC-like cells from mouse PSCs for clinical application. (biomedcentral.com)
  • In fact, only using the OP9 co-culture system combined with hematopoietic related cytokines, we hardly obtained the in vivo functional reconstitution hematopoietic cells from PSCs [ 9 ]. (biomedcentral.com)
  • In addition to circulating NK cells, distinct tissue-resident NK subsets have been identified in various organs. (bvsalud.org)
  • Both new datasets strongly validate our original findings, producing nearly identical developmental trajectories, and exhibiting no evidence of distinct subpopulations of fate-restricted cells in the subventricular zone. (authorea.com)
  • This approach allowed identifying specific chromosomal regions significantly highly or weakly expressed, and clusters of differentially expressed genes and of transcripts related to specific functional modules. (biomedcentral.com)
  • form caused by a germline mutation in ALAS2 (5'-aminolevulinate synthase 2), a gene involved in heme biosynthesis. (msdmanuals.com)
  • Mutation of gene is usually associated with Chediak-Higashi syndrome (CHS), a rare autosomal recessive lysosomal disorder with hematological and immunological abnormalities [13]. (forgetmenotinitiative.org)
  • Besides CHS, mutation in gene is usually one of the important factors that trigger hemophagocytic lymphohistiocytosis, a insufficiency in resistant program function, and life-threatening disease characterized by uncontrolled macrophage and T-cell account activation [14]. (forgetmenotinitiative.org)
  • We demonstrate that enhanced HSF2 expression and the acquisition of HSF2 DNA binding activity are strictly specific for erythroid characteristics of K562 cells. (abo.fi)
  • Then, the genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. (biomedcentral.com)
  • In particular, several genomic studies suggested the existence of relationships between gene expression and genomic position. (biomedcentral.com)
  • The analysis of transcriptome data in the perspective of the genomic organization of genes could certainly shed light not only on the aberrations leading to pathological states but also on the physiological mechanisms of all cellular processes, including cellular differentiation. (biomedcentral.com)
  • Importantly, our results highlight a pivotal role of promoters in determining the transcriptional program activated upon erythroid differentiation. (unisr.it)
  • 5 3 Herein, we have developed and performed a targeted small molecule screen to identify compounds which downregulate α-globin expression. (haematologica.org)
  • This identified IOX1, a pan-histone demethylase inhibitor, which selectively downregulates α-globin expression without perturbing erythroid differentiation or general gene expression, more specifically β-like globin expression. (haematologica.org)
  • Our data show that selective silencing of α-globin expression in erythroid cells is pharmacologically feasible, and IOX1 is a lead compound to developing new therapy to treat β-thalassemia through the novel pathway of downregulating α-globin expression. (haematologica.org)
  • By using RNAi and small molecule inhibitor approaches, we also confirmed that G9a is the major methyltransferase to catalyze H3K27me1 for MMP-9-dependent H3NT proteolysis and trigger the expression of osteoclast-specific genes. (biomedcentral.com)
  • Lists of genes constitutively expressed or silent during myelopoiesis and of genes differentially expressed in commitment phase of myelopoiesis were first identified using a classical data analysis procedure. (biomedcentral.com)
  • Erythroid commitment and differentiation are regulated by the coordinated action of a host of transcription factors, including GATA2 and GATA1. (unisr.it)
  • A progressive loss of H3K27 acetylation and a diminished usage of active enhancers and super-enhancers were observed during erythroid commitment and differentiation. (unisr.it)
  • Expression of this gene is up-regulated in some cancer cell lines, and in embryonic day 15 in mice. (wikipedia.org)
  • focus LY2603618 (IC-83) on lymphoid cell development. (bioinf.org)
  • Further, we innovatively demonstrated that notch signaling pathway is responsible for in vitro CD201 + hematopoietic cell induction from mouse PSCs. (biomedcentral.com)
  • Molecular changes underlying stem cell differentiation are of fundamental interest. (nih.gov)
  • Pathobiology: Cells and Genes;Cellular and Molecular Haematology. (nottingham.ac.uk)
  • Through gene knockout studies he has shown that these molecules act as a type of molecular "Teflon" to make cells more mobile and invasive and also facilitate chemotaxis. (ubc.ca)
  • Our study exhibited that and play pivotal functions in the molecular pathogenesis of MM. This is usually the first statement describing the possible functions of in myelomagenesis and its potential role as a SU 11654 therapeutic target in MM. gene promotes tumorigenesis through constant NAD resynthesis to provide adequate energy for rapidly proliferating malignancy cells [9]. (forgetmenotinitiative.org)
  • Our results offer a even more unique understanding of the jobs of and genes in the molecular pathogenesis of MM. MATERIALS AND METHODS Cell collection The myeloma cell collection RPMI 8226 was purchased from the American Type Culture Collection (ATCC, USA). (forgetmenotinitiative.org)
  • Given these experimental evidences, the integration of high-throughput transcriptional data with gene structural information and functional characteristics represents a major challenge for bioinformatics and computational biology. (biomedcentral.com)
  • Strikingly, cyclin D2-driven lymphomas display transcriptional, immunophenotypic, and functional similarities with B1a B cells. (bvsalud.org)
  • One important cause of impaired erythroid responses in children with SMA is dysregulation in the innate immune response. (ijbs.com)
  • The function of gene in oncogenesis is certainly unsure still, and dysregulation of gene provides hardly ever been defined in Millimeter, nor various other malignancies, before. (forgetmenotinitiative.org)
  • In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. (bvsalud.org)
  • Metazoan development is characterized by complex transcriptional programs specified by gene regulatory networks [1] , [2] . (prolekarniky.cz)
  • However, with the development of gene expression profile and new high-throughput technology, the understanding of the pathogenesis of MDS is getting further and better. (frontiersin.org)
  • Complicated malaria or severe malaria involves the central nervous system (cerebral malaria), the pulmonary system (respiratory failure), the renal system (acute renal failure), and the hematopoietic system (severe anemia). (biomedcentral.com)
  • Here, we examined the expression profile of 108 patients with MDS from the GSE58831 dataset, and identified 22 genes that were significantly associated with overall survival. (frontiersin.org)
  • Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with poor long-term overall survival. (bvsalud.org)
  • We also retrospectively analyzed the overall survival of AML patients with different NFATC1 expression status. (biomedcentral.com)
  • This result suggested an alternative mechanism for the survival of transformed cells. (bioinf.org)
  • Solid as well as blood cancers are associated with overexpression of HOX proteins in the nucleus, which is traditionally a difficult area of the cell to target with conventional drugs. (nottingham.ac.uk)
  • In addition, he identified a number of novel hematopoietic stem cell surface proteins and began analyzing their function. (ubc.ca)
  • The KitW and Kit1SI mutant alleles have similar pleiotropic effects on the development of melanocytes, germ cells, and the hematopoietic system. (bdbiosciences.com)
  • The AM580 induced genes include the HOXA cluster genes and other HSC transcriptional regulators and HSC surface markers. (researchsquare.com)