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Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm Free
Bo Chen1,†, Jiawen Teng1,†, Hongwei Liu1, Xu Pan1, Ya Zhou1, Shu Huang1, Mowen Lai1, Guohui Bian1, Bin Mao1, Wencui Sun1, Qiongxiu Zhou1, Shengyong Yang2, Tatsutoshi Nakahata3, and Feng Ma1,2,4,*
1Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China
2State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610065, China
3Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan
4State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin 300020, China
†These authors contributed equally to this work. *Correspondence to:Feng Ma, E-mail: mafeng@hotmail.co.jp
J Mol Cell Biol, Volume 9, Issue 4, August 2017, 262-273,  https://doi.org/:10.1093/jmcb/mjx032
Keyword: RUNX1/AML1, hematopoiesis, hemogenic endothelium, mesoderm, TGF-β signaling pathway, hESC, inducible expression system

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.


Volume 9, Issue 4
August 2017