Overexpression of GATA2 Enhances Development and Maintenance of Human Embryonic Stem Cell-Derived Hematopoietic Stem Cell-like Progenitors

摘要

GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorlyunderstood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using humanembryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions ofGATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38– HS-like cells. Specifically, GATA2 promotedexpansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cellcycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will helpto elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy togenerate hPSC-derived HSCs.