Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not prior to this.
Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not prior to this.
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DOI：
10.1242/dev.110841
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发表时间：
2014-09
期刊：
影响因子：
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通讯作者：
Medvinsky A
中科院分区：
文献类型：
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作者：
Liakhovitskaia A;Rybtsov S;Smith T;Batsivari A;Rybtsova N;Rode C;de Bruijn M;Buchholz F;Gordon-Keylock S;Zhao S;Medvinsky A
成年动物的造血是由造血干细胞（HSC）维持的，造血干细胞可以自我更新并产生所有的血细胞谱系。AGM区是HSC发育的重要胚胎内位点，大量证据表明，HSC从胚胎背主动脉和胚外大动脉的内皮中出现。然而，这是一个逐步的过程，通过CD 41和CD 45的顺序上调，然后出现完全功能的永久性HSC。虽然Runx 1转录因子在造血干细胞的发育成熟过程中非常重要，但在后期阶段很大程度上是不稳定的;然而，Runx 1在这一多步发育成熟过程中的关键参与点仍不清楚。在这里，我们使用条件可逆敲除策略研究了Runx 1的要求。我们报告Runx 1缺陷并不妨碍VE-cad+ CD 45 − CD 41+细胞的形成，这些细胞在表型上等同于永久性HSC的前体（前HSC I型），但阻断了向随后的CD 45+阶段（前HSC II型）的过渡。这些数据强调了HSC在很短时间内的发育进程是由精确的阶段特异性分子机制调节的。
Haematopoiesis in adult animals is maintained by haematopoietic stem cells (HSCs), which self-renew and can give rise to all blood cell lineages. The AGM region is an important intra-embryonic site of HSC development and a wealth of evidence indicates that HSCs emerge from the endothelium of the embryonic dorsal aorta and extra-embryonic large arteries. This, however, is a stepwise process that occurs through sequential upregulation of CD41 and CD45 followed by emergence of fully functional definitive HSCs. Although largely dispensable at later stages, the Runx1 transcription factor is crucially important during developmental maturation of HSCs; however, exact points of crucial involvement of Runx1 in this multi-step developmental maturation process remain unclear. Here, we have investigated requirements for Runx1 using a conditional reversible knockout strategy. We report that Runx1 deficiency does not preclude formation of VE-cad+CD45−CD41+ cells, which are phenotypically equivalent to precursors of definitive HSCs (pre-HSC Type I) but blocks transition to the subsequent CD45+ stage (pre-HSC Type II). These data emphasise that developmental progression of HSCs during a very short period of time is regulated by precise stage-specific molecular mechanisms.