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Robust hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs

ABSTRACT: The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is supported, recent data suggest that a large fraction of adult blood derives from the yolk sac (YS). Investigating the origins of hematopoiesis before heartbeat onset (i.e. 5-7 somite pairs (sp)) is precluded by a lack of assays that can distinguish dHSC precursors in early embryos. Here, we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2-7sp murine embryonic explants (Em-Ex). dHSC were undetectable in 2-7sp YS explants (YS-Ex). Our work supports a model in which the embryo, not the YS, is the major source of lifelong hematopoiesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE110909 | GEO | 2018/11/13

REPOSITORIES: GEO

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Project description:Yolk sac (YS) hematopoiesis is critical for the survival of the embryo and a major source of tissue-resident macrophages that persist into adulthood. Here we report that the epigenetic regulator Ezh2 is essential for YS hematopoiesis but dispensable for subsequent aorta–gonad–mesonephros (AGM) blood development. Loss of Ezh2 activity in hemogenic endothelium (HE) leads to the generation of phenotypically intact but functionally deficient erythro-myeloid progenitors (EMP). Ezh2 activity is critical at the onset of the endothelial-to-hematopoietic transition generating EMPs but rapidly dispensable after that. We identified a lack of downregulation of Wnt signaling as the primary reason in the generation of non-functional EMPs. Together, our findings demonstrate a critical and specific role of Ezh2 in modulating Wnt signaling during the generation of EMPs from YS HE.

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