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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

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