Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm
Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm
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DOI：
10.1093/jmcb/mjx032
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发表时间：
2017-08-01
影响因子：
5.5
通讯作者：
Ma, Feng
中科院分区：
文献类型：
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作者：
Chen, B.;Teng, Jiawen;Ma, Feng
RUNX1对于最终的造血是绝对必需的，但RUNX1的两种亚型RUNX1b/c的功能尚不清楚。我们建立了可诱导的RUNX1b/c过表达的人胚胎干细胞（hESC）系，其中RUNX1b/c过表达阻止了CD34+细胞的早期出现，从而大大减少了造血干细胞/祖细胞的产生。同时，造血相关因子表达下调。然而，在hESC/AGM-S3细胞共培养中，这种阻断作用从第6天开始消失，证明阻断发生在造血内皮细胞生成之前。这种阻断被转化生长因子(TGF)- β信号通路抑制剂RepSox部分挽救，表明RUNX1b/c与TGF- β通路密切相关。我们的研究结果表明RUNX1b/c在早期造血发育中具有独特的抑制功能，并可能有助于进一步了解其在正常和病变模型中的生物学功能。
RUNX1 is absolutely required for definitive hematopoiesis, but the function of RUNX1b/c, two isoforms of human RUNX1, is unclear. We established inducible RUNX1b/c-overexpressing human embryonic stem cell (hESC) lines, in which RUNX1b/c overexpression prevented the emergence of CD34+ cells from early stage, thereby drastically reducing the production of hematopoietic stem/progenitor cells. Simultaneously, the expression of hematopoiesis-related factors was downregulated. However, such blockage effect disappeared from day 6 in hESC/AGM-S3 cell 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)-beta signaling pathway, indicating a close relationship between RUNX1b/c and TGF-beta 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.