• However, inactivation of MYB severely abrogated proliferation of the primitive erythroid and mixed erythroid-macrophage-megakaryocyte progenitors. (nih.gov)
  • Similar results were observed in Lin-CD34+CD38- hematopoietic stem cells, CD11b+ mature myeloid cells, CD19+ B cells, CD235+ erythroid cells. (confex.com)
  • Using previous findings in healthy cells as a reference, we analyzed scRNA-seq data obtained from patients with myelodysplastic syndrome (MDS) and detected specific alterations of the expression dynamics of genes involved in erythroid differentiation in all patients with MDS such as TRIB2. (cun.es)
  • Additionally, edited CD34 + cells can be further cultured in conditions stimulating lineage-specific differentiation by combining StemSpan™ media with expansion supplements designed for the expansion and differentiation of progenitors to erythroid, myeloid, megakaryocyte, natural killer (NK), or T cell lineages. (stemcell.com)
  • HSC self-renewal capacity and multipotentiality are gradually lost as cells progress through numerous multi- oligo- and uni-lineage intermediates eventually DZNep acquiring either erythroid myeloid or lymphoid identity. (biopaqc.com)
  • Complex transcriptional DZNep networks integrated round the GATA1-PU.1 bimodal switch symbolize a paradigm for myeloid vs erythroid lineage specification 2. (biopaqc.com)
  • The earliest thymic progenitors (ETP) and granulocyte-monocyte progenitors (GMP) long thought to be unilineage retained residual myeloid or lymphoid potential respectively 10 13 14 Importantly recent studies in human wire blood and bone marrow shown the living of early lymphoid-biased progenitors that maintain myeloid but not erythroid potential. (biopaqc.com)
  • The colour of each dot represents expression of myeloid (blue), erythroid (red) and platelet (green) lineage-associated genes. (ox.ac.uk)
  • Cells that were lacZhigh or lacZint were enriched for day 12 spleen colony-forming units and myeloid and erythroid colony-forming cells (CFCs). (ozgene.com)
  • These fractions included >99% of the erythroid and >90% of the myeloid CFCs. (ozgene.com)
  • Our data also suggested that expression of SCL was transient and confined to hematopoietic stem and/or progenitor cells, because the differentiated progeny of most lineages (except the erythroid) were beta-galactosidase-negative. (ozgene.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)
  • Our work reveals that the differentiation of erythroid progenitors is determined by an epigenetic switch which controls the transition between a proliferative state and a commitment towards teminal differentiation. (umontreal.ca)
  • On reception of a differentiation signal, the stochiometry tips in favor of SCL, thus overriding the repressive effect of ETO2 and allowing for activation of a gene expression program controlled by the SCL complex, i.e. erythroid genes and antiproliferative genes (p21Cdkn1a, Gfi-1b). (umontreal.ca)
  • In a murine competitive reconstitution model, Mybl2 knockdown by RNAi to 20-30% of normal levels in multipotent hematopoietic progenitors resulted in clonal dominance of these 'sub-haploinsufficient' cells, which was reflected in all blood cell lineages. (elifesciences.org)
  • Early hematopoiesis is a continuous process in which hematopoietic stem and progenitor cells (HSPCs) gradually differentiate toward specific lineages. (cun.es)
  • 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)
  • In the apex of the hierarchy are hematopoietic stem cells (HSC) which are capable of self-renewal have multi-lineage potential and are responsible for generating all the lineages of hematopoietic cells in the blood. (biopaqc.com)
  • We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compartments, and a marked enhancement of myeloid differentiation at the expense of other lineages. (edu.au)
  • Adenoviral mediated overexpression of HOXB4 in human primitive hematopoietic cells in vitro generates very high levels of HOXB4 within 24 hours of transduction, leading to an increased differentiation towards myeloid lineages, and to a reduction of primitive hematopoietic progenitors, suggesting that the level of HOXB4 expression may determine the fate options following gene transfer. (dissertations.se)
  • This as well as other observations, showing that islet resident macrophages promote beta cell proliferation suggest that islet macrophages are likely important contributors to the function of the pancreatic islet. (wikipedia.org)
  • Circular RNA circ_0040823 inhibits the proliferation of acute myeloid leukemia cells and induces apoptosis by regulating miR-516b/PTEN. (istanbul.edu.tr)
  • 12. Suer I, Kaya M. Is the AURKB gene involved in aml cell proliferation since it is targeted by miR-34a-5p and let-7b-5p? (istanbul.edu.tr)
  • A mutation in this gene resulting in reduced cell proliferation, and impaired cell motility and polarity, and has been identified in patients with primary microcephaly. (cancerindex.org)
  • This cell proliferation appeared to be closely linked to fusion of opposing arch centra. (pkc-inhibitors.com)
  • BCR-ABL oncogene activates multiple cross-talking signal transduction pathways (STP), such as RAS/MEK/ERK, PI3K/Akt, Wnt and STAT5, contributing to abnormal proliferation of clonal cells. (oncotarget.com)
  • From this perspective, the aim of this study was to analyze the expression and activation profile of STP involved in the mechanisms of cell proliferation/quiescence and survival of the progenitor CD34+ cells from chronic phase (CP) CML. (oncotarget.com)
  • In sum, we report that CD34+ cells from CP-CML are characterized by a proteomic and phospho-proteomic profile that promotes quiescence through the inhibition of proliferation and the promotion of survival. (oncotarget.com)
  • WAT is characterised by its capacity to adapt and expand in response to surplus energy through processes of adipocyte hypertrophy and/or recruitment and proliferation of precursor cells in combination with vascular and extracellular matrix remodelling. (springer.com)
  • Depletion of GPR171 with an anti-GPR171 antibody decreased proliferation of lung carcinoma cells and attenuated tumor progression in a mouse xenograft model. (oncotarget.com)
  • Expression of IRS1 , IRS2 or IRS4 in the 32D haematopoietic cell line leads to proliferation of the myeloid progenitor cells and expression of activated IRS4 has recently been demonstrated in the human hepatoblastoma cell line HepG2, with inhibition of IRS4 resulting in diminished growth. (atlasgeneticsoncology.org)
  • Collectively, these findings indicate that correct expression levels of HOXB4 improve proliferative recruitment of HSC in settings demanding high proliferation, for example after bone marrow transplantation. (dissertations.se)
  • Bruggeman SWM, Valk-Lingbeek ME, van der Stoop PPM, Jacobs JJL, Kieboom K, et al: Ink4A and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1-deficient mice. (karger.com)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Previous studies have reported changes in the transcriptional program of genes involved in proliferation, differentiation, apoptosis, and homing when HSPCs were expanded ex vivo. (ox.ac.uk)
  • Mastocytosis and Mast Cell Activation Syndrome Mastocytosis is mast cell proliferation with infiltration of skin or other tissues and organs. (msdmanuals.com)
  • Although proliferation of one or more hematopoietic cell types dominates the clinical picture in each of these disorders, all three are caused by clonal proliferation of a pluripotent hematopoietic stem cell, causing an increased proliferation of normal RBC, WBC, and platelet progenitors in the bone marrow. (msdmanuals.com)
  • ABSTRACT This study examined haematopoietic stem cells of 19 high-risk cases of myelodysplastic syndrome (MDS) for apoptotic and anti-apoptotic signals and cellular proliferation and correlated these with clinical and cytogenetic subtypes, particularly trisomy 8. (who.int)
  • We conclude that downregulation of MYBL2 activity below levels predicted by classical haploinsufficiency underlies the clonal expansion of hematopoietic progenitors in a large fraction of human myeloid malignancies. (elifesciences.org)
  • Abnormalities in this process lead to a group of diseases known as myeloid malignancies, which include acute myeloid leukaemia-in which the bone marrow produces abnormal white blood cells-and myelodysplastic syndromes, which are caused by too few mature blood cells being produced. (elifesciences.org)
  • This deletion is only ever seen in one of their two copies of the chromosome-suggesting that at least some of these genes are essential for survival-but the identity of the gene(s) that are associated with the increased risk of myeloid malignancies is unknown. (elifesciences.org)
  • used gene silencing techniques to reduce the expression of MYBL2 in mice and showed that this induced symptoms of myeloid malignancies in the animals. (elifesciences.org)
  • In addition to revealing a new tumor suppressor gene and its contribution to myeloid malignancies, the study by Heinrichs et al. (elifesciences.org)
  • A better comprehension of cellular hierarchies, epigenetic effects, clonal evolution, and their impact on gene regulation might help to understand disease progression, stratify patient risk, and help to improve the treatment of hematopoietic malignancies in the future. (uni-heidelberg.de)
  • Furthermore, the identification of abnormal regulatory mechanisms associated with myeloid malignancies could be exploited for personalized therapeutic approaches in individual patients. (cun.es)
  • Alterations to genes involved in cellular metabolism and epigenetic regulation are implicated in the pathogenesis of myeloid malignancies. (elsevierpure.com)
  • Use of mIDH inhibitors in combination with drugs with non-overlapping mechanisms of action is especially promising, as such regimens may address the clonal heterogeneity and the multifactorial pathogenic processes involved in mIDH myeloid malignancies. (elsevierpure.com)
  • The Haematopoietic Stem Cell Biology (HSCB) Laboratory is focused on understanding how the normal haematopoietic stem/progenitor hierarchy is disrupted during the development of myeloid malignancies. (ox.ac.uk)
  • The major focus of our research programme is to identify and genetically model leukaemic and pre-leukaemic stem cells in myeloid malignancies. (ox.ac.uk)
  • 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)
  • 3. Identification of somatic and germline genetic abnormalities associated with the development of myeloid malignancies. (ox.ac.uk)
  • 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)
  • TET2 is a well-established tumor suppressor in the context of myeloid malignancies, but its role in lymphoma development has been less clear. (aacrjournals.org)
  • An enlarged HSC pool increases the potential for successive genetic events that drive development of diverse hematopoietic malignancies. (aacrjournals.org)
  • Genomic studies have uncovered silencing TET2 mutations in B-cell and T-cell lymphomas ( 6-8 ), indicating a tumor suppressor role for TET2 in lymphoid malignancies. (aacrjournals.org)
  • Hematopoiesis integrates cytokine signaling, metabolism, and epigenetic modifications to regulate blood cell generation. (nih.gov)
  • Acly was tested for a role in murine hematopoiesis by small-molecule inhibition or genetic deletion in lineage-depleted, c-Kit-enriched hematopoietic stem and progenitor cells from Mus musculus. (nih.gov)
  • As opposed to macrophages in the islet stroma (tissue), whose developmental origin is from the yolk sac (primitive hematopoiesis), islet resident progenitors come from hematopoietic stem cells (HSCs) of the definitive hematopoiesis. (wikipedia.org)
  • MYB is an essential regulator of primitive human hematopoiesis in human pluripotent stem cell differentiation cultures. (nih.gov)
  • MYB is well recognized to be a key regulator of definitive hematopoiesis that plays an important role in the maintenance and multilineage differentiation of hematopoietic stem cells (HSCs). (nih.gov)
  • In acute myeloid leukemia (AML), initiation of tumorigenesis via multiple oncogenic mutations occurs throughout various stages of hematopoiesis that disrupt the corresponding transcriptomic and epigenetic profiles. (uni-heidelberg.de)
  • The results agreed with differential gene expression highlighting many TFs that play a critical role in hematopoiesis, endothelial-to-hematopoietic transition, or leukemic stem cell activation. (uni-heidelberg.de)
  • Trajectory inference revealed that altered gene expression dynamics accompanied cell differentiation, which could explain age-associated changes in hematopoiesis. (cun.es)
  • In summary, we demonstrate that the combination of single cell technologies with computational analysis tools enable the study of a variety of cellular mechanisms involved in complex biological systems such as early hematopoiesis and can be used to dissect perturbed differentiation trajectories associated with perturbations such as aging and malignant transformation. (cun.es)
  • The ability to genetically manipulate hematopoietic stem and progenitor cells (HSPCs) in particular has significantly advanced our understanding of the mechanisms that regulate hematopoiesis and is contributing to the development of novel cellular therapies. (stemcell.com)
  • Here, by using a microarray analysis, we demonstrate that human BM mesenchymal stromal/stem cells (MSCs) in an early osteoinductive stage (e-MSCs) are characterized by unique hematopoiesis-associated gene expression with an enhanced hematopoiesis-supportive ability. (elsevierpure.com)
  • Noteworthy, expression of the hematopoiesis-associated molecules CXCL12 and vascular cell adhesion molecule 1 was remarkably decreased in e-MSCs. (elsevierpure.com)
  • Our findings demonstrate the unique biological characteristics of e-MSCs as hematopoiesis-regulatory stromal cells at differentiation stage between MSCs and osteoprogenitor cells and have significant implications in developing new strategy for using pharmacological osteoinductive treatment to support hematopoiesis in hematopoietic stem and progenitor cell transplantation. (elsevierpure.com)
  • Gene targeting experiments have demonstrated that the transcription factor SCL is essential for primitive and definitive hematopoiesis in the mouse. (ozgene.com)
  • In approximately 15% of patients, however, myelofibrosis is accompanied by significant extramedullary hematopoiesis, hepatosplenomegaly, and transfusion-dependent anemia, which are manifestations of stem cell failure. (basicmedicalkey.com)
  • We compared the HOX expression phenotypes in these AMLs to data from normal bone marrow cells to study the HOX regulatory programs in normal and malignant hematopoiesis. (biotech2012.org)
  • Myeloproliferative neoplasms are clonal proliferations of bone marrow stem cells, which can manifest as an increased number of platelets, red blood cells (RBCs), or white blood cells (WBCs), alone or in combination, in the circulation and sometimes with fibrosis in the bone marrow and extramedullary hematopoiesis (cell production outside the marrow). (msdmanuals.com)
  • Based on their transcriptional profile, we identified changes in the proportions of progenitor compartments during aging, and differences in their functionality, as evidenced by gene set enrichment analysis. (cun.es)
  • In addition, the comparison between transcriptional programs and gene regulatory networks (GRN) regulating normal HSPCs and MDS HSPCs allowed identification of regulons that were specifically active in MDS cases such as SMAD1, HOXA6, POU2F2 and RUNX1 suggesting a role of these TF in the pathogenesis of the disease. (cun.es)
  • In the developing embryo, TFs regulating the assembly/disassembly of transcriptional complexes and ultimately gene expression, are directed by complex extrinsic signalling processes which connect all cells within a multi-cellular organism to their environment. (amegroups.org)
  • Then, the genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. (biomedcentral.com)
  • 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)
  • In the molecular level targeted practical studies of solitary or combined transcription factors possess identified DZNep a relatively DZNep small number of key transcription factors that travel differentiation of progenitor cells by directing the sequential establishment of transcriptional programs essential for terminal differentiation 1. (biopaqc.com)
  • One limitation of this study was the lack of highly purified immature progenitor and stem cell populations which precluded dissection of the very first transcriptional events linked to commitment. (biopaqc.com)
  • In mouse several studies have explained the manifestation of lineage-affiliated transcriptional programs within multilineage progenitors 8-10. (biopaqc.com)
  • 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)
  • Transcriptional profiles at the HOX loci were similar between normal cells and AML samples, and involved Rabbit Polyclonal to LRP10 bidirectional transcription FK 3311 at the center of each gene cluster. (biotech2012.org)
  • Thus, the transcriptional activity of the SCL complex is maintained in check by the ETO2 co-repressor in hematopoietic stem cells and progenitors. (umontreal.ca)
  • Finally, our recent work indicates that myeloid differentiation is controlled by a distinct transcriptional complex which implicates the PU.1, c-Jun and C/EBPb transcription factors. (umontreal.ca)
  • Acute myeloid leukemia (AML) is characterized by developmental arrest, which is thought to arise from transcriptional dysregulation of myeloid development programs. (ox.ac.uk)
  • This complex process is regulated by the interplay of transcription factors with a chromatin environment, both of which provide the epigenetic information maintaining cell-type specific gene expression patterns. (amegroups.org)
  • 1. Kim TK, Gore SD, Zeidan AM. Epigenetic therapy in acute myeloid leukemia: Current and future directions. (istanbul.edu.tr)
  • Epigenetic analysis of a subset of AML samples also identified common regions of chromatin accessibility in AML samples and normal CD34+ cells that displayed differences in methylation depending on HOX expression patterns. (biotech2012.org)
  • These data provide an integrated epigenetic view of the HOX gene loci in primary AML samples, and suggest that HOX expression in most AML samples represents a normal stem cell program that is controlled by epigenetic mechanisms at specific regulatory elements. (biotech2012.org)
  • The epigenetic regulation of spatiotemporal gene expression is crucial for human development. (researchgate.net)
  • Treatments increased the abundance of cell populations that expressed the myeloid integrin CD11b and other markers of myeloid differentiation. (nih.gov)
  • When single-cell RNA sequencing was performed, we found that Acly inhibitor-treated hematopoietic stem and progenitor cells exhibited greater gene expression signatures for macrophages and enrichment of these populations. (nih.gov)
  • The mesoderm gives rise to myeloid progenitor cells, which further differentiate into macrophage populations. (wikipedia.org)
  • Single cells in these populations exhibit different com- stem cell differentiation, Shannon information binations of regulator activity that suggest the presence of multiple theory, entropy configurations of a potential differentiation network as a result of multiple entry points into the committed state. (lu.se)
  • However, harmonizing such datasets requires integration approaches to be not only computationally scalable, but also capable of preserving a wide range of fine-grained cell populations. (nature.com)
  • Cell type prediction revealed extensive malignant cell diversity and a phenotype skewed towards stem- and progenitor-like populations in MLL-EDC4 leukemic cells. (uni-heidelberg.de)
  • We show that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. (ox.ac.uk)
  • Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. (ox.ac.uk)
  • Several recent reports challenged this look at by demonstrating that lymphoid and myeloid fates remain entangled over several early cell populations. (biopaqc.com)
  • To understand how stem lymphoid and myeloid programs are coordinated during hematopoietic differentiation we systematically profiled the transcriptome of MLP in the context of nine additional human being hematopoietic stem and progenitor cell populations for which self-renewal and. (biopaqc.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)
  • 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)
  • Specifically, a variety of other cellular populations have been identified that possess phenotypic characteristics similar to Langerhans cells, including expression of CD207 and Birbeck granules. (medscape.com)
  • Culture of sorted bone marrow populations on stromal cells secreting interleukin-7 or in fetal thymic organ cultures showed that B and T lymphoid progenitors were also present in the lacZhigh and lacZint fractions. (ozgene.com)
  • Lineage analysis of mice bone marrow by FACS showed GFP expression in both the lymphoid (CD19) and myeloid (CD15, CD33) populations. (ox.ac.uk)
  • However, given that bivalent domains can still be observed-albeit in lower proportion-in unipotent cells such as T cells and MEFs, an admixture of cell populations appears to be an unlikely explanation for the observed coexistence of these marks. (researchgate.net)
  • These studies support the lineage priming hypothesis which argues that multipotent progenitors communicate before lineage restriction low levels of genes known to be important determinants of unique fates 11. (biopaqc.com)
  • These progenitors termed multi-lymphoid progenitors (MLP 13 or lymphoid-primed multipotent progenitors (LMPP 15 by analogy with the mouse system 16 are identified as CD34+CD38?Thy1?CD45RA+ 13 15 or by high expression of L-selectin on CD34+ cells 17. (biopaqc.com)
  • They began with five distinct, normal cell types found in the bone marrow in both mice and humans: long-term hematopoietic stem cells (HSCs), short-term HSCs, multipotent progenitors, common myeloid progenitors and granulocyte macrophage progenitors. (news-medical.net)
  • The cells were harvested at different time points for cell-sorting based on the expression of MYB-YFP and CD34 cell surface marker on day 6 and day 12. (nih.gov)
  • We observed that Lin-CD34+CD38+ progenitor cells in 8 out of the 10 MDS patients had higher SALL4 expression levels, while the progenitor cells of normal BM cells did not express SALL4. (confex.com)
  • This Technical Bulletin provides instructions for CRISPR-Cas9 genome editing and maintenance of human CD34 + cells, including optimized pre- and post-editing culture conditions and methods to evaluate genome editing efficiency. (stemcell.com)
  • While CRISPR-Cas9 technology has been successfully applied in numerous cell lines, its application in primary human CD34 + cells has been hampered by challenges in efficient expression and delivery of CRISPR-Cas9 components. (stemcell.com)
  • Early attempts to apply CRISPR-Cas9 for genome editing in CD34 + HSPCs used plasmids for Cas9 and guide RNA (gRNA) expression, which resulted in low targeting efficiency and high toxicity. (stemcell.com)
  • The ArciTect™ CRISPR-Cas9 RNP is then prepared and delivered into CD34 + cells using electroporation, and cells are plated in StemSpan™ SFEM II supplemented with StemSpan™ CD34 + Expansion Supplement post-electroporation. (stemcell.com)
  • e-MSCs supported an enhanced expansion of CD34 + hematopoietic stem and progenitor cells, and generation of myeloid lineage cells in vitro. (elsevierpure.com)
  • However, it can be challenging to differentiate when they are connected with wounded tissue, opposed to when they instruct tissue-specific progenitor cells responsible for the redevelopment of damaged tissue. (techscience.com)
  • e-MSCs exhibited the absence of decreased stemness-associated gene expression, increased osteogenesis-associated gene expression, and apparent mineralization, thus maintaining the ability to differentiate into adipogenic cells. (elsevierpure.com)
  • Lentiviral vector transduction of human hematopoietic progenitor cells has shown transgene expression for extended periods after transplantation into NOD/SCID mice, however, the transduction of a true hematopoietic stem cells with the capacity to differentiate into both myeloid and lymphoid cells has not yet been proven. (ox.ac.uk)
  • This study shows that the lentiviral vector is capable of high efficiency transduction of candidate human hematopoietic stem cells that have the capacity to differentiate into both myeloid and lymphoid cells. (ox.ac.uk)
  • Acute myeloid leukemia patients with DNMT3A mutations exhibit DERARE hypomethylation, elevated HOXB expression, and adverse outcomes. (nih.gov)
  • However, SALL4 expression status and related pathway in bone marrow (BM) cells and relationship with somatic gene mutations in MDS patients has not been explored. (confex.com)
  • In this study, we evaluated the expression of SALL4 and related factors using single-cell mass cytometry (CyTOF) and NanoString technology in MDS patients alongside with target sequence for MDS-related mutations. (confex.com)
  • SALL4 expression was also analyzed in formalin-fixed paraffin-embedded (FFPE) 14 patient samples utilizing two SALL4 probes designed for NanoString technology alongside with target sequence for MDS-related mutations. (confex.com)
  • Both tumor entities harboring FLT3-ITDs or IDH1 mutations showed a more complex composition of cell types along the myeloid differentiation trajectory than MLL fusions. (uni-heidelberg.de)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • 1 These expression systems also pose concerns about safety in clinical translation due to the risk of unwanted genetic mutations and immunogenicity. (stemcell.com)
  • Recurring mutations in isocitrate dehydrogenase (IDH) genes are detected in approximately 20% of adult patients with acute myeloid leukemia (AML) and 5% of adults with myelodysplastic syndromes (MDS). (elsevierpure.com)
  • Ezh2 and Runx1 Mutations Collaborate to Initiate Lympho-Myeloid Leukemia in Early Thymic Progenitors. (ox.ac.uk)
  • In contrast, AMLs with the and gene fusions (27,28) and mutations in (29) have been associated with low or absent HOX gene expression. (biotech2012.org)
  • Most studies have relied on targeted gene expression measurements of only selected HOX genes, or they have focused on AMLs with canonical somatic mutations and/or cytogenetic abnormalities. (biotech2012.org)
  • Frameshift and nonsense mutations occur frequently in CMML, acute myeloid leukemia ( 3 ), and myeloproliferative neoplasm (MPN) cases ( 4 ). (aacrjournals.org)
  • TET2 mutations have been associated with reduced patient survival in acute myeloid leukemia. (aacrjournals.org)
  • Mutations have also been found in the blood of elderly patients without hematopoietic cancers, indicating that TET2 loss alone is not sufficient to trigger leukemic transformation (reviewed in ref. 5 ). (aacrjournals.org)
  • Although mutations in this gene are considered favorable according to current risk stratification guidelines, a large fraction of patients will suffer from relapse, demonstrating the urgent need for new treatment options. (lu.se)
  • Mutations of the Janus kinase 2 ( JAK2 ) gene are responsible for polycythemia vera and a high proportion of cases of essential thrombocythemia and primary myelofibrosis. (msdmanuals.com)
  • Here, our transcriptome and DNA methylome analyses revealed that Hoxb cluster and retinoid signaling genes are predominantly enriched in LT-HSCs, and this coordinate regulation of Hoxb expression is mediated by a retinoid-dependent cis-regulatory element, distal element RARE (DERARE). (nih.gov)
  • Collectively, these findings demonstrate pivotal roles for retinoid signaling and the DERARE in maintaining HSCs and preventing leukemogenesis by coordinate regulation of Hoxb genes. (nih.gov)
  • These patterns were also reflected in the frequency of leukemia-initiating cells in each cell line, with HSCs having the highest frequency and committed progenitors having the lowest. (news-medical.net)
  • Several HOX transcription factors, including HOXB4, are highly expressed in hematopoietic stem cells (HSCs) but are downregulated upon differentiation towards more mature progeny cells. (dissertations.se)
  • 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)
  • Studies in murine models, as well as in human samples, have demonstrated that SALL4 is essential for leukemic cell survival and that SALL4 transgenic mice develop an MDS-like phenotype prior to transformation to AML, suggesting that SALL4 can be a driver of MDS/AML pathogenesis. (confex.com)
  • The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. (edu.au)
  • Enforced expression of HOXB4 dramatically increases the regeneration of murine HSC following transplantation, and enhances the repopulating ability of human SCID repopulating cells. (dissertations.se)
  • Boyer LA, Plath K, Zeitlinger J, Brambrink T, Medeiros LA, et al: Polycomb complexes repress developmental regulators in murine embryonic stem cells. (karger.com)
  • Objective: Acute myeloid leukemia (AML) is a lethal type of cancer associated with dysregulation of progenitor hematopoietic stem cell behavior and its incidence is, unfortunately, increasing. (istanbul.edu.tr)
  • 2. Zhang S, Liu M, Yao Y, Yu B, Liu H. Targeting LSD1 for acute myeloid leukemia (AML) treatment. (istanbul.edu.tr)
  • Identification of circRNA-lncRNA-miRNA-mRNA competitive endogenous rna network as novel prognostic markers for acute myeloid leukemia. (istanbul.edu.tr)
  • Role of circular RNA DLEU2 in human acute myeloid leukemia. (istanbul.edu.tr)
  • Hsa_circ_0012152 and Hsa_circ_0001857 accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. (istanbul.edu.tr)
  • Coexistence of LMPP-like and GMP-like leukemia stem cells in acute myeloid leukemia. (ox.ac.uk)
  • Single-cell transcriptomics uncovers distinct molecular signatures of stem cells in chronic myeloid leukemia. (ox.ac.uk)
  • Every cancer starts with a single cell, and Jackson Laboratory (JAX) researchers have found a precise and reliable way -- whole-genome profiling of open chromatin -- to identify the kind of cell that leads to a given case of leukemia, a valuable key to cancer prognosis and outcome. (news-medical.net)
  • Her lab worked with a mouse model of acute myeloid leukemia (AML) driven by expression of MLL-AF9, a fusion oncogene formed by a chromosome translocation between human chromosomes 9 and 11. (news-medical.net)
  • These results bear out indications in human data that the stage of a progenitor cell when it becomes transformed to leukemia has an impact on its clinical progression, with earlier-stage cell of origin cancers being more aggressive. (news-medical.net)
  • Chronic Myeloid Leukemia (CML) is a stem cell disease sustained by a rare population of quiescent cells which are to some extent resistant to tyrosine kinase inhibitors (TKIs). (oncotarget.com)
  • 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)
  • Interestingly, chemotherapy, including hydroxyurea, has been associated with acute leukemia in JAK2 V617F-negative stem cells in some PV patients. (basicmedicalkey.com)
  • Introduction HOX gene expression is a common feature of acute myeloid leukemia (AML), and is thought to reflect dysregulation of HOX pathways that lead to abnormal self-renewal and the development of leukemia. (biotech2012.org)
  • Decitabine-Vorinostat combination treatment in acute myeloid leukemia activates pathways with potential for novel triple therapy. (nottingham.ac.uk)
  • Inhibition of HOX/PBX dimer formation leads to necroptosis in acute myeloid leukemia cells ONCOTARGET. (nottingham.ac.uk)
  • Our team is composed of postdoctoral fellows, graduate students and technical personnel, whose research theme consists in defining how hematopoietic stem cells integrate various signals to self-renew or to launch a differentiation program and how this code is disrupted in leukemia. (umontreal.ca)
  • Myelodysplastic syndrome (MDS) is a clonal disorder characterized by dyshematopoiesis and high susceptibility to acute myeloid leukemia (AML). (karger.com)
  • We have reported that the expression of BMI1 , a member of PcG, in hematopoietic stem cells or progenitor cells predicts the prognosis of patients with MDS and progression to acute leukemia. (karger.com)
  • Au WY, Fung AT, Ma ES, Liang RH, Kwong YL: Low frequency of FLT3 gene internal tandem duplication and activating loop mutation in therapy-related acute myelocytic leukemia and myelodysplastic syndrome. (karger.com)
  • 2021 , '3101 - MIR-10A AS A THERAPEUTIC TARGET AND PREDICTIVE BIOMARKER FOR MDM2 INHIBITION IN ACUTE MYELOID LEUKEMIA' , Experimental Hematology , 100 , pp. (edu.au)
  • Mutated Nucleophosmin 1 (NPM1) is the most common genetic alteration in acute myeloid leukemia (AML), found in approximately 30% of cases. (lu.se)
  • Acute leukemias Leukemia is a malignant condition involving the excess production of immature or abnormal leukocytes, which eventually suppresses the production of normal blood cells and results in symptoms. (msdmanuals.com)
  • The bias to myeloid differentiation appeared due to insufficient generation of acetyl-CoA, as exogenous acetate to support alternate compensatory pathways to produce acetyl-CoA reversed this phenotype. (nih.gov)
  • Deletion of the DERARE reduced Hoxb expression, resulting in changes to many downstream signaling pathways (e.g., non-canonical Wnt signaling) and loss of HSC self-renewal and reconstitution capacity. (nih.gov)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
  • 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)
  • They act as mediators between multiple growth factor receptors that possess tyrosine kinase activity, such as the insulin and insulin growth factor receptors, and a complex network of intracellular signalling molecules, resulting in activation of, for example, the PI3K and RAS/ERK pathways and subsequent transcription of target genes. (atlasgeneticsoncology.org)
  • By 6 months post-transplantation, the reconstituted mice had developed a clonal myeloproliferative/myelodysplastic disorder originating from the cells with aberrantly reduced Mybl2 expression. (elifesciences.org)
  • In addition, short-term osteoinductive treatment favored in vivo hematopoietic recovery in lethally irradiated mice that underwent BM transplantation. (elsevierpure.com)
  • Mice lacking specific genes also showed deficits in the repopulating ability of hematopoietic cells in competitive transplantation experiments FK 3311 (10C13), although these phenotypes have been variable across studies (14). (biotech2012.org)
  • Transplantation of transduced cells in limiting dilution generated GFP+ lymphoid and myeloid progeny cells that may have arisen from single SRC. (ox.ac.uk)
  • We also demonstrate that C3AR in combination with GPR56 distinguishes the leukemic stem cells (LSCs) in NPM1-mutated AML from the normal hematopoietic stem cells, defining the LSC population, as shown by transplantation into immunodeficient mice. (lu.se)
  • The specific medications administered depend on the choice of therapy and whether it is supportive care only, immunosuppressive therapy, or hematopoietic cell transplantation. (medscape.com)
  • Central venous catheter placement is required before the administration of hematopoietic cell transplantation. (medscape.com)
  • The essence of MDS is damage of In the current work we examined All our patients were of the high-risk colony-forming units [4], but the defect haematopoietic stem cells of high-risk group and none of them was eligible of the haematopoietic stem cells is not MDS cases for apoptotic and anti-apop- for stem cell transplantation. (who.int)
  • We evaluated the expression of SALL4 using single-cell mass cytometry (CyTOF) utilizing 28 antibodies including surface lineage markers and intracellular proteins, such as p53, ki67, c-myc and pAKT to identify SALL4 expressed cells and related pathway in bone marrow (BM) for 10 MDS patients. (confex.com)
  • 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)
  • The recognition of MLP provides a unique opportunity to investigate the molecular mechanisms underlying lymphoid vs myeloid lineage choice in main human being hematopoietic cells. (biopaqc.com)
  • therefore, the phenotype was dependent on TET2 loss occurring earlier in the hematopoietic lineage. (aacrjournals.org)
  • Melinda is highly proficient in the use of in vitro and in vivo assays for normal and malignant hematopoietic stem and progenitor cells, determination of self-renewal, expansion and lineage specific differentiation capabilities, and the use of induced pluripotent stem cells for the investigation of hematopoietic disorders and leukemic progression and the testing of targeted therapeutics. (edu.au)
  • Transposon-mediated rescue of MYB expression in MYB-null cells efficiently restored both the primitive hematopoietic progenitors and immature myeloid cells. (nih.gov)
  • The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). (ox.ac.uk)
  • These data provide a functional correlation between SCL expression and colony-forming ability in immature hematopoietic cells. (ozgene.com)
  • Mutant IDH enzymes have neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked differentiation of hematopoietic progenitor cells. (elsevierpure.com)
  • 02:47 and red blood cells in vitro. (yale.edu)
  • Progenitor cell function may be measured post-modification by in vitro CFU assays. (stemcell.com)
  • Several in vitro scientific studies have demonstrated that chon drocytes related with calcifying cartilage can acquire properties of osteoblasts and therefore are able to change their phenotype from a primarily cartilage www.selleckchem.com/products/Romidepsin-FK228.html synthesizing cell type to a bone synthesizing cell style. (pkc-inhibitors.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)
  • Cost-effective blood cell generation will require novel strategies based on better knowledge of underlying mechanisms driving in vitro development. (biomedcentral.com)
  • In vitro hematopoietic systems might be improved by identifying novel factors from human genetic studies. (biomedcentral.com)
  • In this study, we demonstrate that ATP citrate lyase (Acly), which metabolizes citrate to generate cytosolic acetyl-CoA and is of clinical interest, can regulate chromatin accessibility to limit myeloid differentiation. (nih.gov)
  • Similarly, the single-cell assay for transposase-accessible chromatin sequencing showed increased chromatin accessibility at genes associated with myeloid differentiation, including CD11b, CD11c, and IRF8. (nih.gov)
  • Mechanistically, Acly deficiency altered chromatin accessibility and expression of multiple C/EBP family transcription factors known to regulate myeloid differentiation and cell metabolism, with increased Cebpe and decreased Cebpa and Cebpb. (nih.gov)
  • Analysis from scRNA and scATAC V showed different FLT3 activity/chromatin signatures within clusters of leukemic cells in the relapse that could be explained by midostaurin resistance and the emergence of distinct subclones as detected by scDNA-seq. (uni-heidelberg.de)
  • Third, I characterized how the chromatin accessibility landscape was influenced by IDH1 mutated cells treated ex vivo with targeted therapy compared to IDH1 wild-type cells. (uni-heidelberg.de)
  • In summary, this thesis provides novel insights into the tumorigenesis process in AML by using a systematic and functional analysis approach of the transcriptome and open chromatin in single cells for three major genetically defined AML subgroups. (uni-heidelberg.de)
  • In this review, we highlight the main signals and transcription factors and how they are integrated at the level of chromatin programming and gene expression control. (amegroups.org)
  • Chromatin is the material in the nucleus of the cell that condenses to form chromosomes during cell division, and consists of DNA, proteins called histones and RNA. (news-medical.net)
  • Every type of cell has a characteristic chromatin structure that includes closed chromatin, which is tightly wound around nucleosomes and is relatively inactive, and open chromatin, looser stretches of the material that interact with regulatory elements encoded in DNA. (news-medical.net)
  • Trowbridge hypothesized that analyzing open chromatin in bulk tumor cells could provide a possible improved method to identify cancer cell of origin because of the cell-type specificity of chromatin structure. (news-medical.net)
  • To profile the open chromatin in these distinct AML samples, and compare them to open chromatin patterns in normal cells, Trowbridge collaborated with Duygu Ucar, Ph.D., an assistant professor at JAX who develops computational models to study gene regulation including chromatin structure. (news-medical.net)
  • Together they identified open chromatin signatures and gene expression patterns in AML samples that may allow stem cell-derived AML to be distinguished from progenitor cell of origin AML. (news-medical.net)
  • 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)
  • 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)
  • Histone modifications and chromatin-associated protein complexes are crucially involved in the control of gene expression, supervising cell fate decisions and differentiation. (researchgate.net)
  • Background: Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. (researchgate.net)
  • Chromatin IP against H3K4me1 of induced CD19+ B cells, biological replicate #2. (nih.gov)
  • M, Peterson C. 2018 Haematopoietic stem suggests that during differentiation a stem cell approaches a stable equili- cells: entropic landscapes of differentiation. (lu.se)
  • Accepted: 12 September 2018 tiation progresses, gene expression programmes become more and more constrained and thus the entropy would be expected to decrease. (lu.se)
  • A common deleted region (CDR) in both myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) affects the long arm of chromosome 20 and has been predicted to harbor a tumor suppressor gene. (elifesciences.org)
  • The image shows single cell RNA-sequencing analysis of haematopoietic stem/progenitor cells from a patient with a myeloproliferative neoplasm. (ox.ac.uk)
  • Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease. (edu.au)
  • In addition, functional studies in mice demonstrated that expression of specific HOXA and HOXB genes can lead to expansion of long-term repopulating hematopoietic stem cells and a myeloproliferative phenotype (5C9). (biotech2012.org)
  • Polycythemia Vera Polycythemia vera is a chronic myeloproliferative neoplasm characterized by an increase in morphologically normal red cells (its hallmark), but also white cells and platelets. (msdmanuals.com)
  • [ 3 ] Taken together, these findings have led some to speculate that LCH is not a specific disease of epidermal Langerhans cells, but rather one of mononuclear phagocyte dysregulation. (medscape.com)
  • These mice show a reduced beta cell mass as well as developmental defects. (wikipedia.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)
  • 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)
  • First, I characterized changes in the transcriptome and classified developmental stages of leukemic cells carrying MLL-EDC4 fusions along the hematopoietic stem cell to the myeloid trajectory compared to other MLL fusions. (uni-heidelberg.de)
  • However, all developmental processes originate from pluripotent precursor cell types. (amegroups.org)
  • We also highlight recent studies identifying the cis -regulatory elements such as enhancers at the global level and explain how their developmental activity is regulated by the cooperation of cell-type specific and ubiquitous transcription factors with extrinsic signals. (amegroups.org)
  • Central to this is the transient increase in H3K4-trimethylation at developmental genes during G1, thereby creating a 'window of opportunity' for cell-fate specification. (researchgate.net)
  • In addition, although some studies have shown that HOX genes are expressed in both AML samples and normal hematopoietic cells (25), the precise patterns of expression in normal versus malignant hematopoietic cells remains unclear. (biotech2012.org)
  • The rapid emergence of large-scale atlas-level single-cell RNA-seq datasets presents remarkable opportunities for broad and deep biological investigations through integrative analyses. (nature.com)
  • 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)
  • We propose that powerful machine-learning techniques based on 'joint manifold learning', often used in the 'alignment' of massive imaging datasets to recognized shared high-dimensional features, can be used to recognize shared cellular phenotypes across single cell datasets. (authorea.com)
  • GSE94591, GSE116617, and GSE163386) were used to investigate dysregulated expressions of circular RNAs (circRNAs), and the GSE142699 and GSE142698 datasets were analyzed to detect dysregulated expressions of microRNAs (miRNAs) and mRNAs, respectively. (istanbul.edu.tr)
  • Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
  • To identify putative causal genes from these data, we performed computational modeling using available genome-wide association datasets for platelet and red blood cell traits. (biomedcentral.com)
  • In this issue of Cancer Discovery , Dominguez and colleagues report their findings on the mechanistic link between TET2 mutation and germinal center (GC) B-cell transformation (3). (aacrjournals.org)
  • Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)
  • The gene reporter system showed that MYB is specifically expressed during hematopoietic commitment in the earliest primitive blood cells. (nih.gov)
  • We found that MYB was not required for initial hematopoietic commitment of nascent mesoderm and emergence of primitive, yolk sac-type human hematopoietic progenitors. (nih.gov)
  • A cell-dose limiting dilution into secondary transplant recipients showed lentiviral transduction of more primitive SRC. (ox.ac.uk)
  • Comparing the cell surface expression on NPM1-mutated AML cells to primitive (CD34+ CD38-) normal bone marrow cells, we identified the complement receptor C3AR as specifically expressed in NPM1-mutated AML. (lu.se)
  • Mast cell activation syndrome is increased and inappropriate activation of mast cells without clonal. (msdmanuals.com)
  • We examined the expression of a panel of 17 known SALL4 downstream target genes. (confex.com)
  • Moreover, transcription factors and their target genes form vast interacting gene regulatory networks which can be exquisitely stable. (amegroups.org)
  • This protein forms a tetrameric complex with the alpha subunit, and stimulates transcription of target genes. (nih.gov)
  • This suggests that in most cases primary CD34+ AML is a progenitor disease where LSCs acquire abnormal self-renewal potential. (ox.ac.uk)
  • Mesenchymal stem cells (MSCs) are multipotent stromal cells capable of self-renewal and exhibit multilineage differentiation properties. (techscience.com)
  • Initial studies of HOX gene expression in human hematopoietic cells showed that expression is largely restricted to hematopoietic stem/progenitor cells (1C4), which are uniquely capable of long-term self-renewal. (biotech2012.org)
  • Work in knockout mouse models has shown that TET2 loss enhances hematopoietic stem cell (HSC) self-renewal, expanding the HSC pool (reviewed in refs. (aacrjournals.org)
  • Recently, evidence has been accumulating on the molecular mechanism underlying self-renewal of stem cells. (karger.com)
  • Specifically, we have been focusing on Polycomb-group (PcG) genes, which play an important role in supporting self-renewal. (karger.com)
  • We examined whether CPM is expressed by hematopoietic and stromal cells and could degrade stromal cell-derived factor (SDF)-1a, a potent chemoattractant for hematopoietic stem/progenitor cells (HSPC). (razikurd.ir)
  • Cells were cultured for up to 5 days in IMDM medium supplemented with 10% FCS/2% PSG/β-me and IL-7 and SCF cytokines on S17 feeder cells in the presence of 1 ug/mL doxycycline, or alternatively, in alpha-MEM medium in the presence of cytokines and on Tst-4 stromal cells. (nih.gov)
  • MLL fusions, except for MLL-EDC4, generally conferred a more differentiated phenotype predominantly consisting of monocytes/macrophage CD14-like and promonocyte-like cells. (uni-heidelberg.de)
  • The remarkable contributions of these organelles to innate and adaptive immunity, shape cell phenotype and modulate their functions during infection, after trauma and in the setting of inflammatory disease. (biomed.news)
  • Therefore, in addition to epidermal Langerhans cells, other potential cellular origins for LCH include dermal langerin + dendritic cells, lymphoid tissue-resident langerin + dendritic cells, and monocytes that can be induced by local environmental stimuli to acquire a Langerhans cell phenotype. (medscape.com)
  • The correct cell must be chosen for its phenotype, cell characteristics and biological functions. (biomedcentral.com)
  • The islet resident macrophage was first identified in 1979 as an antigen-presenting cell (APC), which expresses major histocompatibility complexes (MHCs). (wikipedia.org)
  • The working group of the Histiocyte Society divided histocytic disorders into three groups: (1) dendritic cell histiocytosis, (2) macrophage-related disorders, and (3) malignant histiocytosis. (medscape.com)
  • The programmes governing the function and fate of cells are to a large extent driven by the coordinated activity of transcription factors forming complex and dynamic gene regulatory networks (GRNs). (lu.se)
  • The activities of transcription factors and other genes involved in cell fate decisions can be measured by a number of different gene expression quantification experiments. (lu.se)
  • Additionally, scATAC-seq allows to map the binding of transcription factors (TF) and infer cell-specific regulatory networks. (uni-heidelberg.de)
  • Initial gene expression analysis on 38 human being hematopoietic cell subtypes recognized gene modules and transcription factors circuits active in stem and progenitor cell-enriched fractions and reused HIRS-1 in terminally differentiated cells 7. (biopaqc.com)
  • We have utilized the GEPIA tool to determine the Overall Survival of the hub genes. (istanbul.edu.tr)
  • Arguments supporting the reactive nature of LCH include the occurrence of spontaneous remissions, the extensive elaboration of multiple cytokines by dendritic cells and T-cells (the so-called cytokine storm) in LCH lesions, and the good survival rate in patients without organ dysfunction. (medscape.com)
  • Our results showed that CP-CML CD34+ progenitors were characterized by significant lower phosphorylation of proteins involved in the regulation of growth and cell survival, such as tyrosine kinases of the Src family and members of STAT family, and by a significant higher phosphorylation of p53 (Ser15), compared to normal CD34+ cells from healthy donors. (oncotarget.com)
  • Mechanistically, stimulation of C3AR-expressing cells with C3a, the ligand of C3AR, leads to activation of ERK1/2 and increased survival of AML cells, suggesting that this is an important signaling axis in this subtype of AML. (lu.se)
  • Based on principal component analysis and gene expression profiling we demonstrate that CD34+ HSPCs that do not undergo ex vivo expansion are transcriptionally similar to minimally differentiated AML blasts. (ox.ac.uk)
  • Finally, we show that antibodies directed against C3AR efficiently elicit NK cell-mediated killing of primary AML cells ex vivo, highlighting C3AR as a candidate therapeutic target in NPM1-mutated AML. (lu.se)
  • Our model built from platelet trait GWAS loci reliably distinguished sentinel GWAS SNPs, as well as platelet-relevant genes and loci. (biomedcentral.com)
  • have uncovered a key tumor suppressor among those genes frequently lost on chromosome 20. (elifesciences.org)
  • The modified cells are able to expand more robustly than normal cells, and this dominance induced by downregulation of the tumor suppressor increases the risk of malignancy. (elifesciences.org)
  • highlights the importance of gene dosage in mediating the effects of tumor suppressors. (elifesciences.org)
  • The cancer cells that emerge are referred to as blasts and share biological features from these disease-specific alterations and patterns associated with differentiation and the tumor cell of origin. (uni-heidelberg.de)
  • Sequencing methods that analyze the transcriptome (scRNA-seq) and epigenome (scATAC-seq) are ideally suited to resolve tumor cell heterogeneity as well as non-malignant cell types in the microenvironment. (uni-heidelberg.de)
  • Within the same prostate cancer cell line model, a whole new HDAC inhibitor, H6CAHA, sup pressed the expression of BRCA1 mRNA, and when used in Inhibitors,Modulators,Libraries mixture with g radiation, prevented the development of tumor xenografts. (pkc-inhibitors.com)
  • Knowing the cell of origin of cancer cells can provide insight into tumor subtypes and possibly diagnostic and therapeutic benefit,' says JAX Assistant Professor Jennifer Trowbridge, Ph.D., the lead author of the study published on July 11 in Nature Communications . (news-medical.net)
  • But existing methods to identify cell of origin from bulk tumor cell samples have been unsuccessful. (news-medical.net)
  • These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • Knockout mice for the CSF-1 gene cause islets to be devoid of resident macrophages. (wikipedia.org)
  • Moreover, injection of modified cells from these animals into healthy mice also induced symptoms in the recipients. (elifesciences.org)
  • The AML that developed from these different cells of origin had different penetrance and aggressiveness when engrafted in mice, with the stem cell-derived lines being the most aggressive and the committed progenitor lines the least. (news-medical.net)
  • To study the functional properties of hematopoietic cells expressing SCL, we have generated mutant mice (SCLlacZ/w) in which the Escherichia coli lacZ reporter gene has been "knocked in" to the SCL locus, thereby linking beta-galactosidase expression to transcription from the SCL promoter. (ozgene.com)
  • Bone marrow cells from heterozygous SCLlacZ/w mice were sorted into fractions expressing high, intermediate and low levels of beta-galactosidase (designated lacZhigh, lacZint, and lacZneg). (ozgene.com)
  • Studies in our knockout mice reveal that deficiency of HOXB4 leads to a hypocellularity in hematopoietic organs and impaired proliferative capacity. (dissertations.se)
  • In this study we transplanted lentivirally transduced human cord blood CD34+ cells in limiting dilution into NOD/SCID mice. (ox.ac.uk)
  • FACS analysis of bone marrow derived from these mice revealed that 5% and 64% of cells expressed GFP and 0% and 74% of the CFU-GM derived from these mice express the transgene. (ox.ac.uk)
  • Islet resident macrophages are the predominant myeloid cell of the pancreatic islets of langerhans. (wikipedia.org)
  • Islet resident macrophages depend on the expression of colony stimulating factor (CSF1). (wikipedia.org)
  • As the most abundant innate immune cells, monocyte-derived macrophages play a pivotal role in the inflammatory response, cholesterol metabolism, and foam cell formation. (biomed.news)
  • Langerhans cell histiocytosis (LCH) is a group of idiopathic disorders characterized by the presence of cells with characteristics similar to bone marrow-derived Langerhans cells juxtaposed against a backdrop of hematopoietic cells, including T-cells, macrophages, and eosinophils. (medscape.com)
  • Aging and myeloid malignant transformation are characterized by changes in the composition and regulation of HSPCs. (cun.es)
  • In this study, we used single cell RNA sequencing (scRNAseq) to characterize an enriched population of human hematopoietic stem and progenitor cells (HSPCs) obtained from young and elderly healthy individuals. (cun.es)
  • However, the majority of samples expressed a canonical set of HOXA and HOXB genes that was nearly identical to the expression signature of normal hematopoietic stem/progenitor cells (HSPCs). (biotech2012.org)
  • Hematopoietic stem and progenitor cells (HSPCs) isolated from human blood are frequently used as a normal comparator in AML studies. (ox.ac.uk)
  • This was confirmed by comparing the cell cycle status of the AML blasts and the HSPCs. (ox.ac.uk)
  • The generation of receptors specific for antigens is a unique and complex process that generates 10 12 specific receptors for each cell type of the adaptive immune system, including T and B cells. (medscape.com)
  • Various cell types can process and present these antigens to T cells, or antigens may be soluble and bound to B-cell receptors. (medscape.com)
  • B19 is the primary etiologic agent causing TAC in patients with chronic hemolytic anemias (e.g., sickle cell disease, hemoglobin SC disease, hereditary spherocytosis, alpha-thalassemia, and autoimmune hemolytic anemia) (22,23). (cdc.gov)
  • Chronic lymphoid leukaemia and hairy cell leukaemia due to chronic exposure to benzene: Report of three cases. (cdc.gov)
  • To explore the role of MYB in human hematopoietic development we have inactivated the gene by bi-allelic TALEN-supported gene targeting in several lines of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), and subjected these cells to hematopoietic differentiation in well-defined cell culture conditions. (nih.gov)
  • 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)
  • Here we show that bivalent domains and chromosome architecture for bivalent genes are dynamically regulated during the cell cycle in human pluripotent cells. (researchgate.net)