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Overexpression of GATA2 enhances development and maintenance of human embryonic stem cell-derived hematopoietic stem cell-like progenitors

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干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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http://data.iscr.ac.cn/Article?id=3289f40a3ff61d88742efd0724ded5cd
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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 HSC-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- HSC-like cells. Specifically, GATA2 promoted expansion of hemogenic precursors via the EHT and then helped to maintain HSC-like cells in a quiescent state by arresting the cell cycle at G0/G1 phase. RNA-sequencing showed that hPSC-derived-HSC-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 generate hPSC-derived HSCs.
提供机构:
Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College
创建时间:
2022-02-20
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