Embryonic definitive hematopoiesis generates hematopoietic stem and progenitor cells (HSPCs) essential for establishment and maintenance of the adult blood system. This process requires the specification of a subset of vascular endothelial cells to become blood-forming, or hemogenic, and the subsequent endothelial-to-hematopoietic transition to generate HSPCs therefrom. The mechanisms that regulate these processes are under intensive investigation, as their recapitulation in vitro from human pluripotent stem cells has the potential to generate autologous HSPCs for clinical applications. In this review, we provide an overview of hemogenic endothelial cell development and highlight the molecular events that govern hemogenic specification of vascular endothelial cells and the generation of multilineage HSPCs from hemogenic endothelium. We also discuss the impact of hemogenic endothelial cell development on adult hematopoiesis.
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