Inducible overexpression of RUNX1b/c in human embryonic stem cells blocks early hematopoiesis from mesoderm

• 来源期刊: 分子细胞生物学报（英文版）
• 年，卷（期）: 2017,（4）
• 页码范围: 262-273
• 页数: 12页
• 语种: 英文
• DOI: 10.1093/jmcb/mjx032

摘要

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.