Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The transition from quiescent to activated states in human hematopoietic stem cells is governed by dynamic 3D genome reorganization [Low-C]

ABSTRACT: Life-long blood production requires long-term hematopoietic stem cells (LT-HSC) - marked by stemness states involving quiescence and self-renewal - to transition into activated short-term HSC (ST-HSC) with reduced stemness. As few transcriptional changes underlie this transition, we used single-cell and bulk ATAC-seq on human HSC and stem/progenitor subsets (HSPC) to uncover chromatin accessibility signatures, one including LT-HSC (LT/HSPC signature) and another excluding LT-HSC (Act/HSPC signature). These signatures inversely correlated during early hematopoietic commitment and differentiation. The Act/HSPC signature contains CTCF binding sites mediating 351 chromatin interactions, engaged in ST-HSC but not LT-HSC, enclosing multiple stemness pathway genes active in LT-HSC and repressed in ST-HSC. CTCF silencing derepressed stemness genes, restraining quiescent LT-HSC from transitioning to activated ST-HSC. Hence, 3D chromatin interactions centrally mediated by CTCF, endow a gatekeeper function that governs the earliest fate transitions HSC make by coordinating disparate stemness pathways linked to quiescence and self-renewal.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159287 | GEO | 2020/11/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

RNA-seq of uncultured CD112high and CD112low and cultured long-term (LT) and short-term (ST) human hematopoietic stem cells (HSC) overexpressing INKA-1

Project description:RNA-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) and cultured and lentiviral transduced (CTRL, INKA1-OE) LT- and short-term HSC from umbilical cord blood We performed RNA-sequencing to elucidate the biological pathways (1) altered by INKA1 overexpression in LT-HSC and ST-HSC that may contribute to the induced transient restraint in generating proliferative hematopoietic output in vivo and in vitro; and (2) that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated indicated subpopulations from 3 independent human umbilical cord blood pools and subjected them either to RNA-sequencing directly or following culture, lentiviral transduction and purification of the transduced cell fractions. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

2021-03-25 | GSE148883 | GEO

ATAC-seq of uncultured CD112high and CD112low long-term(LT) human hematopoietic stem cells (HSC) from umbilical cord blood

Project description:We performed ATAC-sequencing to elucidate the chromatin accessibility that underlie the differential in vitro priming and regeneration phenotypes of CD112high and CD112low LT-HSC. Therefore, we prospectively isolated these subpopulations from 3 independent human umbilical cord blood pools and subjected to ATAC-sequencing directly. We show that distinct subsets of human LT-HSC respond differently to regeneration-mediated stress and that INKA1 governs these distinct stemness states where CD112low LT-HSC are marked by an alternative state of quiescence with high INKA1 and low H4K16ac preserving self-renewal and regenerative capacity upon successive rounds of regeneration-mediated stress.

2021-04-13 | GSE172005 | GEO

Transcription profiling of mouse normal LT-HSC vs ST-HSC

Project description:Self-renewal is a defining characteristic of stem cells, however the molecular pathways underlying its regulation are poorly understood. Here we demonstrate that conditional inactivation of the Pbx1 proto-oncogene in the hematopoietic compartment results in a progressive loss of long-term hematopoietic stem cells (LT-HSCs) that is associated with concomitant reduction in their quiescence, leading to a defect in the maintenance of self-renewal as assessed by serial transplantation. Transcriptional profiling revealed that multiple stem cell maintenance factors are perturbed in Pbx1-deficient LT-HSCs, which prematurely express a large subset of genes, including cell cycle regulators, normally expressed in non-self-renewing multipotent progenitors. Experiment Overall Design: LT-HSC (Lin-cKit+Sca1+CD34-CD135-) and ST-HSC (Lin-cKit+Sca1+CD34+CD135-) cells were prospectively sorted from the BM of MxCre-.Pbx1f/f control mice harvested 4 weeks after the last injection of poly(I:C).

2008-06-20 | E-GEOD-9189 | biostudies-arrayexpress

Analysis of DNA methylation changes in normal human hematopoietic stem and progenitor cells

Project description:DNA methylation analysis on purified human long-term and short-term hematopoietic stem cells (LT-HSC, ST-HSC), common myeloid and megakaryocyte-erythrocyte progenitor cells (CMP, MEP) using HELP arrays. FACS-purified hematopoietic stem and progenitor cell (HSPC) subsets were analyzed for changes in DNA methylation using NimbleGen HELP microarrays. Analysis of DNA methylation of bone marrow-derived HSPC subsets of healthy human donors.

2014-02-07 | E-GEOD-52151 | biostudies-arrayexpress

Analysis of RNA expression changes in normal human hematopoietic stem and progenitor cells

Project description:RNA expression analysis on purified human long-term and short-term hematopoietic stem cells (LT-HSC, ST-HSC), common myeloid and megakaryocyte-erythrocyte progenitor cells (CMP, MEP) using microarrays. FACS-purified hematopoietic stem and progenitor cell (HSPC) subsets were analyzed for changes in RNA expression using NimbleGen gene expression microarrays. Analysis of RNA expression of bone marrow-derived HSPC subsets of healthy human donors.

2014-02-07 | E-GEOD-52150 | biostudies-arrayexpress

Analysis of DNA methylation changes in normal human hematopoietic stem and progenitor cells

2014-02-07 | GSE52151 | GEO

Analysis of RNA expression changes in normal human hematopoietic stem and progenitor cells

2014-02-07 | GSE52150 | GEO

Chromatin remodeling and dynamics of hematopoietic stem cells and progenitors

Project description:Hematopoietic stem cells (HSCs) have the capability to self-renew and differentiate into all blood cell lineages. How chromatin state regulates self-renewal and differentiation of HSC is not fully understood. Here, we provided the first global landscape of chromatin state in long term (LT)-HSCs, short term (ST)-HSCs and multipotent progenitor (MPP) by ATAC-seq analysis. We discovered that the promoter regions of genes that control cell cycle, and several important miRNAs were maintained as open chromatin state in HSCs. In addition, we found that promoter-TSS regions of many genes were occupied by nucleosomes in LT/ST-HSC and they become open chromatin regions in MPP. Furthermore, we uncovered 166 known transcription factors (TFs) including C/EBPs, GABPA, and FLI1can access to the promoter open chromatin in HSCs, and quarter of them displayed cell type-specific manner. Among them, we identified DNA cis-element of Krüppel-like factor family (KLF9, KLF10 and KLF14) were specifically enriched in LT-HSC. Meanwhile, we found that 8299 enhancers are established concomitantly with the formation of open chromatin sites, and they can be accessed by 153 TFs including GABPA, CTCF and RNUX1/RUNX2. Near hundred TF-binding motif are enriched in both promoter and enhancers, indicating they may direct the interaction between promoters and enhancers. Finally, we found 21.7% poised enhancers were preset in LT/ST-HSCs, and became active enhancers in MPP. Together, our finding provides new insightinto how chromatin state and transcriptionalregulatory networkare remodeledin promoter and enhancer regions during the differentiation of LT/ST-HSC to MPP.

2017-06-05 | GSE84959 | GEO

Stem cell fate choices are regulated through antagonistic control of lysosomes by MYC and TFEB [RNA-Seq 2]

Project description:We show that lysosomes are antagonistically controlled by TFEB and MYC to balance catabolic and anabolic processes required for activating LT-HSC and guiding their lineage fate. TFEB-mediated induction of the endolysosomal pathway for membrane receptor degradation limits LT-HSC metabolic and mitogenic activation; this promotes quiescence and self-renewal and governs erythroid-myeloid commitment. By contrast, MYC engages biosynthetic processes while repressing lysosomal catabolism to drive LT-HSC activation. Collectively, our study identifies lysosomes as a central regulatory hub for proper and coordinated stem cell fate determination.

2021-07-31 | GSE153912 | GEO

Stem cell fate choices are regulated through antagonistic control of lysosomes by MYC and TFEB [ATAC-Seq]

2021-07-31 | GSE153910 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data