Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chromatin remodeling and dynamics of hematopoietic stem cells and progenitors

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE84959 | GEO | 2017/06/05

SECONDARY ACCESSION(S): PRJNA335747

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcription profiling of Pairwise comparisons of purified mouse LT-HSC, ST-HSC and MPP

Project description:Pairwise comparisons of purified mouse LT-HSC, ST-HSC and MPP.

2005-09-09 | E-SMDB-3457 | biostudies-arrayexpress

Gene expression profiling of LT-HSCs and ST-HSCs conditionally expressing MLL-ENL

Project description:We have developed a new conditional transgenic mouse showing that MLL-ENL, at an endogenous-like expression level, induces leukemic transformation selectively in LT-HSCs. To investigate the molecular mechanism of leukemic transformation in LT-HSCs conditionally expressing MLL-ENL, we preliminarily performed comprehensive gene expression profiling of CreER-transduced LT-HSCs and ST-HSCs using cDNA microarray analysis. For initial screening of candidate genes invloved in the leukemic transformation, total RNA was extracted from colony-forming cells derived from LT-HSCs and ST-HSCs transduced with CreER or mock. Four samples were analyzed, and CreER-transduced LT/ST-HSC-derived cells were compared with mock-transduced LT/ST-HSC-derived cells, while CreER/mock-transduced LT-HSC-derived cells were compared with CreER/mock-transduced ST-HSC-derived cells.

2013-07-17 | E-GEOD-48539 | biostudies-arrayexpress

LIGHT/LTβR signaling regulates self-renewal and differentiation of hematopoietic and leukemia stem cells

Project description:Purpose: The goal of this study is to compare NGS-derived transcriptome profiling (RNA-seq) of Ltbr-deficient and -proficient LT/ST-HSCs isolated from chimeric mice. Methods: Transcriptomic profiles of Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice 6 weeks after reconstitution were assessed in triplicate by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using TaqMan and SYBR Green assays. Results: We mapped about 60 million sequence reads per sample to the mouse genome (GRCm38 - mm10) and identified expressed transcripts in Ltbr-/- and Ly5.1 LT/ST-HSCs isolated from chimeric mice. RNA-seq. data confirmed stable expression of known housekeeping genes. Differentially expressed genes between the Ltbr-/- and Ly5.1 LT/ST-HSCs were identified with a fold change ≥1.5 and FDR p-value <0.05. Conclusions: Our study represents the first detailed transcriptome analysis of Ltbr-deficient and -proficient LT/ST-HSCs, with biologic replicates, generated by RNA-seq. technology. Our results show that Ltbr signaling regulates HSC proliferation and differentiation. Evaluation of mRNA content in Ltbr-/- LT/ST-HSCs revealed that Ltbr-deficiency enhances HSC proliferation, differentiation, cell cycle and reduces the activity of canonical NFkB signaling.

2020-10-23 | GSE141206 | GEO

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

Project description: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.

2020-11-23 | GSE159287 | GEO

Expression data of freshly isolated and sorted HSC populations from murine fetal liver or adult bone marrow [array]

Project description:We isolated murine fetal liver and murine adult bone marrow and FACS sorted LT-HSCs, ST-HSCs and MPPs. We used global expression analysis by microarray to compare regulated genesets in different HSC populations in fetal and adult.

2023-04-30 | GSE173158 | GEO

RNA-sequencing analysis of murine Hematopoietic Stem Cells treated with Nicotinamide Riboside

Project description:LT-HSC and ST-HSCs were FACS sorted (>10^4cells per sample), cultured for two days in presence or absence of 1 mM NR and total RNA extracted

2019-01-17 | GSE125211 | GEO

Effect of bioengineered niches on perivascular stem cell phenotype.

Project description:Long-term reconstituting haematopoietic stem cells (LT-HSCs) are used to treat blood disorders via allogeneic stem cell transplantation (alloSCT), to engraft and repopulate the blood system. The very low abundance of LT-HSCs and their rapid differentiation during in vitro culture hinders their clinical utility. Previous developments using stromal feeder layers, defined media cocktails, and bioengineering have enabled HSC expansion in culture, but of mostly short-term HSCs (ST-HSC) and progenitor populations at the expense of naïve LT-HSCs. Here, we report the creation of a bioengineered LT-HSC maintenance niche that recreates physiological extracellular matrix organisation, using soft collagen type-I hydrogels to drive nestin expression in perivascular stromal cells (PerSCs or pericytes). We demonstrate that nestin, which is expressed by HSC-supportive bone marrow stromal cells, is cytoprotective and, via regulation of metabolism, is important for HIF-1 expression in PerSCs. When CD34+ve HSCs were added to the bioengineered niches comprising nestin/HIF-1 expressing PerSCs, LT-HSC numbers were maintained with normal clonal and in vivo reconstitution potential, without media supplementation. We provide proof-of-concept that our bioengineered niches can support the survival of CRISPR edited HSCs. Successful editing of LT-HSCs ex vivo can have potential impact on the treatment of blood disorders.

2024-04-25 | GSE265789 | GEO

Low-C on Human CB-derived LT-HSC and ST-HSC

Project description:Low-C was performed upon human cord-blood long-term hematopoietic stem cells (LT-HSC) and short-term hematopoietic stem cells (ST-HSC). This was used to demonstrate that chromatin conformation changes associated with LT-HSC activation are enriched in ST-HSC.

| EGAS00001004744 | EGA

miR-125a Confers Multi-Lineage Long-Term Repopulating Stem Cell Activity to Murine and Human Hematopoietic Progenitors

Project description:Umbilical cord blood (CB) is a non-invasive, convenient and broadly used source of hematopoietic stem cells (HSCs) for allogeneic stem cell transplantation. However, limiting numbers of HSCs remain a major constraint for its clinical application. One feasible option would be to expand HSCs to improve therapeutic outcome, however available protocols and the molecular mechanisms governing the self-renewal of HSC are unclear. Here we show that ectopic expression of a single miRNA, miR-125a, in purified murine and human multipotent progenitors (MPP) resulted in increased self-renewal and robust long-term multi-lineage repopulation in transplanted recipient mice. Using quantitative proteomics and Western blot analysis, we identified a restricted set of miR-125a targets which revealed the involvement of the MAP kinase signaling pathway in conferring long-term repopulating capacity to multipotent progenitors in human and mice. Our findings offer the innovative potential to use MPP with enhanced self-renewal activity to augment limited sources of HSC to improve clinical protocols.

2017-01-11 | PXD003931 | Pride

Time-course analysis of transcriptomes of human long-term (LT) and short-term (ST) hematopoietic stem cells (HSC) after xenotransplantation

Project description:Here we tracked transcriptional changes in LT, ST-HSC and MLP after transplantation into immunocompromised mice. We show that LT- and ST-HSC activate similar pathways upon transplantation but they modulate distinct sets of genes.

2015-02-20 | GSE58299 | 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