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

Abstract

Summary: GATA2 is essential for the endothelial-to-hematopoietic transition (EHT) and generation of hematopoietic stem cells (HSCs). It is poorly understood how GATA2 controls the development of human pluripotent stem cell (hPSC)-derived HS-like cells. Here, using human embryonic stem cells (hESCs) in which GATA2 overexpression was induced by doxycycline (Dox), we elucidated the dual functions of GATA2 in definitive hematopoiesis before and after the emergence of CD34+CD45+CD90+CD38– HS-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HS-like cells in a quiescent state by regulating cell cycle. RNA sequencing showed that hPSC-derived HS-like cells were very similar to human fetal liver-derived HSCs. Our findings will help to elucidate the mechanism that controls the early stages of human definitive hematopoiesis and may help to develop a strategy to generate hPSC-derived HSCs. : In this article, Professor Ma and his colleagues at IBT of CAMS & PUMC show that overexpression of GATA2 promoted expansion of hemogenic precursors through EHT, and thereafter enhanced the maintenance of HS-like cells in dormancy by cell-cycle arrest. hESC-derived HS-like cells were highly similar to human fetal liver (FL) HSCs. Keywords: GATA2, hESCs, hematopoietic stem cells, definitive hematopoiesis, cell cycle