CNRS, UPMC, UMR7622, Bat C, 6(ème) étage, Case 24, 9, quai Saint Bernard, 75252 Paris Cedex 05, France.
Blood Cells Mol Dis. 2013 Dec;51(4):232-8. doi: 10.1016/j.bcmd.2013.07.004. Epub 2013 Aug 7.
The embryonic dorsal aorta plays a pivotal role in the production of the first hematopoietic stem cells (HSCs), the founders of the adult hematopoietic system. HSC production is polarized by being restricted to the aortic floor where a specialized subset of endothelial cells (ECs) endowed with hemogenic properties undergo an endothelial-to-hematopoietic production resulting in the formation of the intra-aortic hematopoietic clusters. This production is tightly time- and space-controlled with the transcription factor Runx1 playing a key role in this process and the surrounding tissues controlling the aortic shape and fate. In this paper, we shall review (a) how hemogenic ECs differentiate from the mesoderm, (b) how the different aortic components assemble coordinately to establish the dorso-ventral polarity, and (c) how this results in the initiation of Runx1 expression in hemogenic ECs and the initiation of the hematopoietic program. These observations should elucidate the first steps in HSC commitment and help in developing techniques to manipulate adult HSCs.
胚胎背主动脉在产生第一批造血干细胞(HSCs)中起着关键作用,HSCs 是成人造血系统的创始人。HSC 的产生受到限制,仅限于主动脉底部,在那里具有造血特性的内皮细胞(ECs)的一个专门亚群经历内皮到造血的产生,导致主动脉内造血簇的形成。这种产生受到严格的时间和空间控制,转录因子 Runx1 在这个过程中起着关键作用,周围组织控制主动脉的形状和命运。在本文中,我们将回顾:(a)造血内皮细胞如何从中胚层分化;(b)不同的主动脉成分如何协调组装以建立背腹极性;(c)这如何导致造血内皮细胞中 Runx1 表达的启动和造血程序的启动。这些观察结果应该阐明 HSC 承诺的第一步,并有助于开发操纵成人 HSC 的技术。