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Overexpression of GATA2 Enhances Development and Maintenance of Human Embryonic Stem Cell-Derived Hematopoietic Stem Cell-like Progenitors
Author(s) -
Ya Zhou,
Yonggang Zhang,
Bo Chen,
Yong Dong,
Yimeng Zhang,
Bin Mao,
Pan Xu,
Mowen Lai,
Yijin Chen,
Guohui Bian,
Qiongxiu Zhou,
Tatsutoshi Nakahata,
Jiaxi Zhou,
Min Wu,
Feng Ma
Publication year - 2019
Publication title -
stem cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.207
H-Index - 76
ISSN - 2213-6711
DOI - 10.1016/j.stemcr.2019.05.007
Subject(s) - biology , stem cell , embryonic stem cell , haematopoiesis , progenitor cell , gata2 , microbiology and biotechnology , hematopoietic stem cell , cancer research , genetics , gene
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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