Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.
Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter.
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DOI：
10.1038/nature07619
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发表时间：
2009-02-12
期刊：
影响因子：
64.8
通讯作者：
Speck, Nancy A.
中科院分区：
文献类型：
--
作者：
Chen, Michael J.;Yokomizo, Tomomasa;Zeigler, Brandon M.;Dzierzak, Elaine;Speck, Nancy A.
HSC是成人造血系统的创始细胞，因此在发育期间指导其生成的分子程序的知识对于再生造血策略是重要的。Runx 1是小鼠孕体血管区域-主动脉、卵黄和脐动脉、卵黄囊和胎盘中HSC生成所需的关键转录因子。据认为，HSC通过动脉内簇的形成从血管内皮细胞中出现，并且Runx 1在从“生血内皮”向HSC的转变过程中起作用。在这里，我们表明，Runx 1的活性血管内皮钙粘蛋白（VEC）阳性内皮细胞的条件删除，动脉内集群，造血祖细胞，HSC的形成确实是必不可少的。相反，Runx 1在表达Vav的细胞中是不需要的，Vav是HSC中表达的第一个泛造血基因之一。总的来说，这些数据表明，Runx 1的功能是必不可少的内皮细胞造血祖细胞和造血干细胞的形成从脉管系统，但其需求结束后或之前Vav表达。
HSCs are the founder cells of the adult hematopoietic system, and thus knowledge of the molecular program directing their generation during development is important for regenerative hematopoietic strategies. Runx1 is a pivotal transcription factor required for HSC generation in the vascular regions of the mouse conceptus - the aorta, vitelline and umbilical arteries, yolk sac and placenta. It is thought that HSCs emerge from vascular endothelial cells through the formation of intra-arterial clusters and that Runx1 functions during the transition from ‘hemogenic endothelium’ to HSCs. Here we show by conditional deletion that Runx1 activity in vascular endothelial cadherin (VEC) positive endothelial cells is indeed essential for intra-arterial cluster, hematopoietic progenitor, and HSC formation. In contrast, Runx1 is not required in cells expressing Vav, one of the first pan-hematopoietic genes expressed in HSCs. Collectively these data show that Runx1 function is essential in endothelial cells for hematopoietic progenitor and HSC formation from the vasculature, but its requirement ends once or before Vav is expressed.
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影响因子：
20.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.0402270102
发表时间：
2005-01-04
影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.93.8.3444
发表时间：
1996-04-16
影响因子：
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作者：
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通讯作者：
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