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

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. Single cell global gene expression analysis of Em-Ex- and YS-Ex-CD31+CD45+c-Kit+CD41- cells.