ATAC-seq data from EB-HSPC after AM580 treatment compared to DMSO-treated EB
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76681 | GEO | 2016/05/16
SECONDARY ACCESSION(S): PRJNA308423
REPOSITORIES: GEO
Similar Datasets
Project description:RA signalling regulated endothelial to hematopoietic transition and HSC generation.
2016-05-16 | GSE76682 | GEO
Project description:RA signalling regulated endothelial to hematopoietic transition and HSC generation. EB- or FL-derived HSPC were profiled before (d0) or after (d6) 6 days of treatment with 0.2uM AM580 on OP9, and after 6 additional days of expandion of OP9 (d12) without treatment.
2016-05-16 | E-GEOD-76682 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSC) rely on a unique regulatory machinery that facilitates life-long blood production and enables reconstitution of the entire hematopoietic system upon transplantation. However, the biological processes governing human HSC self-renewal and engraftment ability are poorly understood and challenging to recapitulate ex vivo to facilitate robust human HSC expansion. We discovered a novel HSC regulatory protein, MYCT1 (MYCT target 1), that is selectively expressed in endothelial cells (EC) and undifferentiated human HSPCs but becomes drastically downregulated during HSC culture. Lentiviral knockdown of MYCT1 in human foetal liver and cord blood HSPCs revealed a critical role for MYCT1 in governing human HSPC expansion and engraftment ability. Single cell RNAseq of human CB HSPCs after MYCT1 knockdown and overexpression revealed that MYCT1 governs HSC functional competence and modulates cellular properties essential for HSC stemness, such as low mitochondrial metabolic activity. Indeed, restoring the compromised MYCT1 expression in cultured human CB HSPCs improved ex vivo expansion of the most undifferentiated human HSPCs and enhanced their engraftment ability. We found that MYCT1 is localized in the endosomal membrane and interacts with vesicle trafficking regulators and signalling machinery essential for HSC and EC function. Loss of MYCT1 led to excessive endocytosis and hyperactive signalling responses to cytokines, whereas restoring MYCT1 expression in cultured CB HSPCs balanced the abnormal endocytosis associated with prolonged culture and fine-tuned signalling responses. Our work identifies MYCT1-moderated endocytosis and environmental sensing as an essential regulatory mechanism required to preserve human HSC stemness, and pinpoints silencing of MYCT1 as a critical contributor to the dysfunction of cultured human HSCs that needs to be addressed to improve human HSC culture strategies.
2024-04-15 | PXD042257 | Pride
Project description:To decode the complexed mechanism controlling HSC expansion, from the viewpoint of systems biology, we performed spatial transcriptome analysis by dissecting the whole hematopoietic organ, CHT.
2019-04-23 | GSE120509 | GEO
Project description:Hematopoietic stem cells (HSCs) are considered a heterogeneous cell population. In an attempt to further resolve the HSC compartment, we characterized a retinoic acid (RA) reporter mouse line. Sub-fractionation of the HSC compartment in RA-CFP reporter mice demonstrated that RA-CFP-dim HSCs were largely non-proliferative and displayed superior engraftment potential in comparison to RA-CFP-bright HSCs. Gene expression analysis demonstrated higher expression of RA-target genes in RA-CFP-dim HSCs, contrasting the RA-CFP reporter expression, but both RA-CFP-dim and –bright HSCs responded efficiently to ATRA in vitro. Single-cell RNA-sequencing of >1,200 HSCs showed that differences in cell cycle activity constitutedthe main driver of transcriptional heterogeneity in HSCs. Moreover, further analysis of the single-cell RNA-seq data revealed that stochastic low-level expression of distinct lineage-affiliated transcriptional programs is a common feature of HSCs. Collectively, this work demonstrates the utility of the RA-CFP reporter line as a tool for the isolation of superior HSCs.
2018-06-21 | GSE108155 | GEO
Project description:A subset of osteoblasts functions as a key component of the hematopoietic stem cell niche. But it is still unclear that the precise cellular and molecular contribution of endosteal cell populations on the HSC supportive microenvironment. We purified the endosteal cells and subdivided them into mesenchymal progenitor cells (MPCs: PDGF-Ra(+)Sca-1(+)) and two osteoblast populations (PDGF-Ra(-)Sca-1(-) and PDGF-Ra(+)Sca-1(-)). In this study, to clarify the characteristics of these fractionated cells in detail, gene expression analysis were performed using the GeneChip Mouse Genome Array 430 2.0 (Affymetrix). The bone fragments of femur and tibiae were treated with collagenase and endosteal cells were obtained. For enrichment of non-hematopoietic and non-endothelial population, CD45(-)CD31(-)Ter119(-) population was isolated and then the expressions of Sca-1 and PDGF-Ra was analyzed by FACS. FACS analysis showed that CD45(-)CD31(-)Ter119(-) cells were subdivided into PDGF-Ra(+)Sca-1(+), PDGF-Ra(-)Sca-1(-) and PDGF-Ra(+)Sca-1(-). These three populations were sorted and RNA samples were used for amplification, labeling, and hybridization to independent arrays.
2010-08-10 | E-GEOD-17570 | biostudies-arrayexpress
Project description:Long-term hematopoietic stem cells (LT-HSCs) are responsible for lifelong maintenance and regeneration of the blood system. Loss of LT-HSC function is a major contributor to decline in hematopoietic function with aging, leading to increased rate of infection, poor vaccination response, and increased risk of hematologic malignancies. While cellular and molecular hallmarks of LT-HSC aging have been defined, a barrier to achieving the goal of extending healthy hematopoietic function into older age is the lack of understanding of the nature and timing of the initiating events that cause LT-HSC aging. Here we show that hallmarks of LT-HSC aging and decline in hematopoietic function accumulate by middle age in mice, and that the hematopoietic cell-extrinsic bone marrow (BM) microenvironment at middle age is necessary and sufficient to cause LT-HSC aging. Using unbiased transcriptome-based approaches, we identify decreased production of IGF1 by mesenchymal stromal cells (MSC) in the local middle-aged BM microenvironment as a factor causing LT-HSC aging and show that direct stimulation of middle-aged LT-HSCs with IGF1 rescues hallmarks of aging. Together, our study demonstrates that the initiating events causing LT-HSC and hematopoietic aging emerge by middle age and are caused by hematopoietic cell-extrinsic changes in the BM microenvironment. Declining IGF1 in the BM microenvironment at middle age represents a compelling target for intervention using prophylactic therapies to effectively extend healthspan and prevent decline in hematopoietic function during aging.
2021-01-12 | GSE164609 | GEO
Project description:Purpose:To identify genes involved in the DEK regulating chromatin accessibility of hematopoietic stem cells (HSC) in mice, we performed ATAC-Sequence of HSC freshly sorted from mice.
2021-02-22 | GSE166432 | GEO
Project description:Activation of mostly quiescent hematopoietic stem cells (HSC) is a prerequisite for life-long blood production1, 2. This process requires major molecular adaptations to meet the regulatory and metabolic requirements for cell division3-8. The mechanisms governing cellular reprograming upon stem cell activation and their subsequent return to quiescence are still not fully characterized. Here, we describe a role for chaperone-mediated autophagy (CMA)9, a selective form of lysosomal protein degradation, in sustaining adult HSC function. CMA is required for stem cell protein quality control and upregulation of fatty acid metabolism upon HSC activation. We identify that CMA activity decreases with age in HSC and show that genetic or pharmacological activation of CMA can restore functionality of old HSC. Together, our findings provide mechanistic insights into a new role for CMA in sustaining quality control, appropriate energetics and overall long-term hematopoietic stem cell function. Our work supports that CMA may be a promising therapeutic target to enhance hematopoietic stem cell function in conditions such as aging or stem cell transplantation.
2021-03-05 | PXD022196 | Pride
Project description:Expansion for hematopoietic cells from umbilical cord blood is a strategy for use this cell source in clinic transplants, however, it is important to know about the genomic changes that can occur in expanded cells. In order to detect global expression profiles changes in hematopoietic stem and progenitors cells generated in vitro, we analyzed hematopoietics populations obtained by FACS in fresh from umbilical cord blood. HSC (fHSC) was defined as CD34+ CD38- CD71- CD45RA- Lin- and were cocultured with stromal cell line OP-9 plus FL, SCF, IL3, IL6, TPO, GMCSF and G-CSF by 7 days, after time we repurified HSC population by FACS using same immunophenotype (ivHSC). In other hand, fresh erythroid progenitors cells (fEPC) were identified as CD34+CD38+CD71+CD45RA- Lin- and fresh myeloid progenitors cells (fMPC) were identified as CD34+CD38+CD71-CD45RA+Lin-. In vitro progenitors cells (ivEPC and ivMPC) were obtained by culturing fHSC in Stemspan serum-free media plus SCF, TPO, IL6, FL and IL3 by 10 days, after time cells were repurified by FACS using same immunophenotype for fresh progenitors. In vitro generated cells were compared with their corresponding fresh population cells.
2018-06-05 | GSE107497 | GEO