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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2833-2842
Number of pages10
JournalJournal of Experimental Medicine
Volume210
Issue number13
DOIs
StatePublished - Dec 2013

Fingerprint

Dive into the research topics of 'Gata2 cis-element is required for hematopoietic stem cell generation in the mammalian embryo'. Together they form a unique fingerprint.

Cite this