Renin-angiotensin System and Hemangioblast Development from Human Embryonic Stem Cells

Human embryonic stem cells (hESCs) offer the opportunity to create a novel source of blood cells for transfusion, transplantation and cancer immunotherapy. Identification of sequential progenitors leading to blood development, as well as a detailed understanding of the molecular mechanisms of hematopoietic lineage specification and diversification from hESCs, will be critical to advance technologies for large-scale production of blood cells and in vitro generation of hematopoietic stem cells. Multiple lines of evidence suggest that hematopoiesis, both in vivo during embryogenesis and in vitro from hESCs, is initiated from hemangioblasts; cells with the potential to generate both hematopoietic and endothelial cells. However, the phenotypic and functional properties of hemangioblasts remain largely unknown. The paper from Zambidis et al. is the first demonstration that hemangioblasts generated from hESCs express angiotensin-converting enzyme (CD143). More importantly, the current study demonstrates that the renin-angiotensin system plays a critical role in the hemangioblast fate decision to produce either blood or endothelial cells. These findings could be exploited for developing novel cellular and drug therapies for hematological and vascular diseases.