2. Academic Validation
  3. 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

  • J Mol Cell Biol. 2017 Aug 1;9(4):262-273. doi: 10.1093/jmcb/mjx032.
B Chen 1,  Jiawen Teng 1,  Hongwei Liu 1,  X Pan 1,  Y Zhou 1,  Shu Huang 1,  Mowen Lai 1,  Guohui Bian 1,  Bin Mao 1,  Wencui Sun 1,  Qiongxiu Zhou 1,  Shengyong Yang 2,  Tatsutoshi Nakahata 3,  Feng Ma 1 2 4
Affiliations

Affiliations

  • 1 Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Chengdu 610052, China.
  • 2 State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610065, China.
  • 3 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan.
  • 4 State Key Laboratory of Experimental Hematology, CAMS & PUMC, Tianjin 300020, China.
PMID: 28992293 DOI: 10.1093/jmcb/mjx032
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.

Keywords

RUNX1/AML1; TGF-β signaling pathway; hESC; hematopoiesis; hemogenic endothelium; inducible expression system; mesoderm.

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