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

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2019 Jun 11

PMID 31178416

Citations 21

Authors

Ya Zhou

Yonggang Zhang

Bo Chen

Yong Dong

Yimeng Zhang

Bin Mao

Xu Pan

Mowen Lai

Yijin Chen

Guohui Bian

Qiongxiu Zhou

Tatsutoshi Nakahata

Jiaxi Zhou

Min Wu

Feng Ma

Affiliations

Soon will be listed here.

Abstract

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 CD34CD45CD90CD38 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.

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