Wu Yinyu, Hirschi Karen K
Departments of Medicine and Genetics, Yale Cardiovascular Research Center, Vascular Biology and Therapeutics Program, and Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA; email:
Department of Cell Biology, University of Virginia, Charlottesville, Virginia 22908, USA; email:
Annu Rev Physiol. 2021 Feb 10;83:17-37. doi: 10.1146/annurev-physiol-021119-034352. Epub 2020 Oct 9.
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.
胚胎期确定性造血产生造血干细胞和祖细胞(HSPCs),这些细胞对于成人血液系统的建立和维持至关重要。这一过程需要特定的血管内皮细胞亚群分化为造血细胞,即造血内皮细胞,随后通过内皮-造血转化从中产生HSPCs。调控这些过程的机制正在深入研究中,因为从人多能干细胞在体外重现这些过程有可能产生用于临床应用的自体HSPCs。在这篇综述中,我们概述了造血内皮细胞的发育,并强调了控制血管内皮细胞造血特化以及从造血内皮细胞产生多谱系HSPCs的分子事件。我们还讨论了造血内皮细胞发育对成人造血的影响。