摘要
RUNX1 绝对为 RUNX1b/c 的权威的造血作用，而是功能被要求，人的 RUNX1 的二 isoforms，是不清楚的。我们建立了可诱导的 RUNX1b/c-overexpressing 人的胚胎的干细胞(hESC ) 线，在 RUNX1b/c， overexpression 阻止了 CD34+ 房间的出现早舞台，急速地从而减少造血的干细胞的生产。同时，造血作用相关的因素的表示是 downregulated。然而，如此的阻塞效果从在 hESC/AGM-S3 房间合作文化的白天 6 消失了，证明阻塞发生在 hemogenic endothelial 房间的产生前。这阻塞被 RepSox 部分救，转变生长因素(TGF ) 的一个禁止者 - 发信号的小径，显示在 RUNX1b/c 和 TGF- 小径之间的一种靠近的关系。我们的结果在早造血作用的开发建议 RUNX1b/c 的一个唯一的禁止的函数并且可以在正常和 diseased 模型帮助它的生物函数的进一步的理解。
RUNXI is absolutely required for definitive hematopoiesis, but the function of RUNXlb/c, two isoforms of human RUNX1, is unclear. We established inducible RUNXlb/c-overexpressing human embryonic stem cell （hESC） lines, in which RUNXlb/c overexpression prevented the emergence of CD34＋ cells from early stage, thereby drastically reducing the production of hematopoi- etic stem/prognnitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 ceU co-cultures, proving that the blockage occurred before the generation of hemogenic endothelial cells. This blockage was partially rescued by RepSox, an inhibitor of the transforming growth factor （TGF）-β signaling pathway, indicating a close relationship between RUNX1b/c and TGF-β pathway. Our results suggest a unique inhibitory function of RUNX1b/c in the development of early hematopoiesis and may aid further understanding of its biological function in normal and diseased models.
基金
This work was supported by the National Program on Key Basic Research Project of China （973 Program
2015CB964902）, the National Natural Science Foundation of China （NSFC
H81170466 and H81370597）, and the CAMS Initiatives for Innovative Medicine （2016-12M-1-018） awarded to F.M.
