| Literature DB >> 28992293 |
B Chen1, Jiawen Teng1, Hongwei Liu1, X Pan1, Y Zhou1, Shu Huang1, Mowen Lai1, Guohui Bian1, Bin Mao1, Wencui Sun1, Qiongxiu Zhou1, Shengyong Yang2, Tatsutoshi Nakahata3, Feng Ma1,2,4.
Abstract
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)-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.Entities:
Keywords: RUNX1/AML1; TGF-β signaling pathway; hESC; hematopoiesis; hemogenic endothelium; inducible expression system; mesoderm
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Year: 2017 PMID： 28992293 DOI： 10.1093/jmcb/mjx032
Source DB: PubMed Journal: J Mol Cell Biol ISSN： 1759-4685 Impact factor: 6.216