Kanz Dirk, Konantz Martina, Alghisi Elisa, North Trista E, Lengerke Claudia
Department of Stem Cell and Regenerative Biology, Harvard University, Boston, Massachusetts.
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Ann N Y Acad Sci. 2016 Apr;1370(1):97-108. doi: 10.1111/nyas.13030. Epub 2016 Mar 25.
During development, hematopoietic stem cells (HSCs) are formed in a temporally and spatially restricted manner, arising from specialized endothelial cells (ECs) in the ventral wall of the dorsal aorta within the evolutionary conserved aorta-gonad-mesonephros region. Our understanding of the processes regulating the birth of HSCs from ECs has been recently advanced by comprehensive molecular analyses of developing murine hematopoietic cell populations complemented by studies in the zebrafish model, with the latter offering unique advantages for genetic studies and direct in vivo visualization of HSC emergence. Here, we provide a concise review of the current knowledge and recent advances regarding the cellular origin and molecular regulation of HSC development, with particular focus on the process of endothelial-to-hematopoietic transition and its primary regulator, the Notch signaling pathway.
在发育过程中,造血干细胞(HSCs)以时间和空间受限的方式形成,起源于进化保守的主动脉-性腺-中肾区域背主动脉腹侧壁的特化内皮细胞(ECs)。最近,通过对发育中的小鼠造血细胞群体进行全面的分子分析,并辅以斑马鱼模型研究,我们对调控内皮细胞产生造血干细胞过程的理解取得了进展,后者在基因研究和造血干细胞出现的直接体内可视化方面具有独特优势。在此,我们简要综述了关于造血干细胞发育的细胞起源和分子调控的当前知识及最新进展,特别关注内皮-造血转化过程及其主要调节因子Notch信号通路。