期刊
CELL REPORTS
卷 20, 期 7, 页码 1597-1608出版社
CELL PRESS
DOI: 10.1016/j.celrep.2017.07.067
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类别
资金
- NIH grants [P01 HL094374, R01 HL084642, U01 HL100405, P01 GM81619]
- Fondation Leducq Transatlantic Network of Excellence
- [T32 HL007312]
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR+/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of bloodforming endothelial cells. Using HOPX reporter and knockout hESCs, we show that HOPX regulates blood-formation. Loss of HOPX does not impact endothelial fate specification but markedly reduces primitive hematopoiesis, acting at least in part through failure to suppress Wnt/beta-catenin signaling. Thus, chromatin state analysis permits identification of regulators of mesodermal specification, including a conserved role for HOPX in governing primitive hematopoiesis.
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