4.8 Article

SOX17 integrates HOXA and arterial programs in hemogenic endothelium to drive definitive lympho-myeloid hematopoiesis

期刊

CELL REPORTS
卷 34, 期 7, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2021.108758

关键词

-

资金

  1. National Institutes of Health [R01HL142665, U01HL134655, P51OD011106, P30 CA014520]
  2. Charlotte Geyer Foundation

向作者/读者索取更多资源

The research findings suggest that SOX17 is a key regulator in linking arterial and HOXA programs in hemogenic endothelium (HE) in humans, playing a crucial role in the specification of HE with robust lympho-myeloid potential. This understanding may contribute to better programming of hematopoietic stem cell fate from human pluripotent stem cells.
SOX17 has been implicated in arterial specification and the maintenance of hematopoietic stem cells (HSCs) in the murine embryo. However, knowledge about molecular pathways and stage-specific effects of SOX17 in humans remains limited. Here, using SOX17-knockout and SOX17-inducible human pluripotent stem cells (hPSCs), paired with molecular profiling studies, we reveal that SOX17 is a master regulator of HOXA and arterial programs in hemogenic endothelium (HE) and is required for the specification of HE with robust lympho-myeloid potential and DLL4(+)CXCR4(+) phenotype resembling arterial HE at the sites of HSC emergence. Along with the activation of NOTCH signaling, SOX17 directly activates CDX2 expression, leading to the upregulation of the HOXA cluster genes. Since deficiencies in HOXA and NOTCH signaling contribute to the impaired in vivo engraftment of hPSC-derived hematopoietic cells, the identification of SOX17 as a key regulator linking arterial and HOXA programs in HE may help to program HSC fate from hPSCs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据