Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo

Xin Gao, Kirby D. Johnson, Yuan I. Chang, Meghan E. Boyer, Colin N. Dewey, Jing Zhang, Emery H. Bresnick*

*此作品的通信作者

研究成果: Article同行評審

100 引文 斯高帕斯(Scopus)

摘要

The generation of hematopoietic stem cells (HSCs) from hemogenic endothelium within the aorta, gonad, mesonephros (AGM) region of the mammalian embryo is crucial for development of the adult hematopoietic system. We described a deletion of a Gata2 cis-element (+9.5) that depletes fetal liver HSCs, is lethal at E13-14 of embryogenesis, and is mutated in an immunodeficiency that progresses to myelodysplasia/leukemia. Here, we demonstrate that the +9.5 element enhances Gata2 expression and is required to generate long-term repopulating HSCs in the AGM. Deletion of the +9.5 element abrogated the capacity of hemogenic endothelium to generate HSC-containing clusters in the aorta. Genomic analyses indicated that the +9.5 element regulated a rich ensemble of genes that control hemogenic endothelium and HSCs, as well as genes not implicated in hematopoiesis. These results reveal a mechanism that controls stem cell emergence from hemogenic endothelium to establish the adult hematopoietic system.

原文English
頁(從 - 到)2833-2842
頁數10
期刊Journal of Experimental Medicine
210
發行號13
DOIs
出版狀態Published - 12月 2013

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