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

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.

• Authors: Xin Gao, Kirby D Johnson, Yuan-I Chang, Meghan E Boyer, Colin N Dewey, Jing Zhang, Emery H Bresnick
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 210 Issue 13 Pg. 2833-42 (Dec 16 2013) ISSN: 1540-9538 [Electronic] United States
• PMID: 24297994 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• GATA2 Transcription Factor
• Gata2 protein, mouse

Topics

• Animals
• Aorta (embryology)
• Cell Separation
• Enhancer Elements, Genetic
• Female
• Flow Cytometry
• GATA2 Transcription Factor (metabolism)
• Gene Expression Regulation, Developmental
• Gene Regulatory Networks
• Genomics
• Gonads (embryology)
• Hematopoietic Stem Cells (cytology)
• Male
• Mesonephros (embryology)
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Mutation
• Stem Cells (cytology)