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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [Hi-C]

ABSTRACT: We performed multi-omics exploration of early aorta endothelial cells (AECs), hemogenic endothelial cells (HECs), pre-HSCs and long-term HSCs (LT-HSCs) along definitive HSC emergence in mouse embryos. Globally, we find that most hematopoiesis related enhancers were already pre-activated at the beginning, followed by strengthened looping structure of enhancers and promoters. After the stronger interactions forming, enhancers can be further activated to promote hematopoiesis gene expressions. Specifically, the important hematopoietic transcription factor (TF) RUNX1 can mediate enhancer-promoter interactions, which starts from a subset of early AECs, prior to appearance of HECs. Thus, the stepwise and asynchrony cooperation of multi-omics and TFs in definitive hematopoiesis has been revealed holistically in vivo. It may also reflect general epigenetic regulation models of developmental processes.

ORGANISM(S): Mus musculus

PROVIDER: GSE161326 | GEO | 2021/12/12

REPOSITORIES: GEO

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Pre-configuring chromatin architecture with histone modifications guide hematopoietic stem cell formation in mouse embryos [ChIP-seq]

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Project description:GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HSC-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38- HSC-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HSC-like cells in a quiescent state by arresting the cell cycle at G0/G1 phase. RNA-sequencing showed that hPSC-derived-HSC-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to generate hPSC-derived HSCs.

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