Hematopoietic stem cell emergence in the human embryo and fetus.

Two waves of hematopoietic stem cell generation take place in the first month of human gestation. The first one has long been known to occur in the yolk sac; only recently was another one identified that results in the development, from the 27th day, of clusters of hematopoietic cells on the ventral endothelium of the aorta and vitelline artery. This latter, intra-embryonic phase of blood cell progenitor production is undoubtedly local since its presumptive territory of occurrence, the para-aortic splanchnopleura, is endowed with blood-forming potential in vitro from, at least, day 19 of development. The first multipotent, lympho-myeloid stem cells emerge within that intra-embryonic territory, whereas the yolk sac only produces myeloid precursor cells devoid of lymphoid potential. The forerunners of the hematopoietic stem cells born to intra-embryonic arteries appear to migrate from the splanchnopleura as KDR(+) angio-hematopoietic cells that colonize the ventral wall of the aorta to give rise to hematogenous endothelium. All these results indicate that stem cells for human definitive hematopoiesis emerge within the embryo, in the walls of truncal arteries, from splanchnopleural ancestors and through a vascular endothelial intermediate stage. Less expectedly, blood-forming endothelial cells were also encoutered in the embryonic and fetal liver and in the fetal and, even, adult bone marrow, suggesting that a filiation between vascular and hematopoietic cells may persist during the whole life.