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Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
Published on: December 3, 2015
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Gata2 is required for HSC generation and survival
Emma de Pater1, Polynikis Kaimakis, Chris S Vink
1Erasmus Medical Center, Erasmus Stem Cell Institute, 3000 CA Rotterdam, Netherlands.
The Journal of Experimental Medicine
|December 4, 2013
Summary
GATA2 is crucial for generating hematopoietic stem cells (HSCs) from endothelial cells and for HSC survival. This transcription factor plays a vital role throughout HSC development, unlike RUNX1.
Area of Science:
- Hematopoiesis
- Developmental Biology
- Stem Cell Biology
Background:
- Hematopoietic stem cell (HSC) generation is key for regenerative medicine.
- GATA2 is a known hematopoietic transcription factor, but its role in HSC generation was unclear.
- HSCs originate from endothelial cells in embryonic vasculature.
Purpose of the Study:
- To investigate the function of GATA2 in HSC generation and survival.
- To determine the stage-specific requirements for GATA2 in HSC development.
Main Methods:
- Specific deletion of Gata2 in endothelial cells (Vec-expressing).
- Specific deletion of Gata2 in hematopoietic cells (Vav-expressing).
- Analysis of HSC generation, long-term repopulating capacity, and survival.
Main Results:
- Gata2 deletion in endothelial cells impaired HSC generation and reduced intra-aortic hematopoietic clusters.
- Gata2 deletion in hematopoietic cells compromised HSC survival.
- GATA2 is essential for both HSC generation and survival, unlike RUNX1.
Conclusions:
- GATA2 is indispensable for the endothelial-to-hematopoietic transition during HSC generation.
- GATA2 is also critical for the survival of generated HSCs.
- GATA2 has a unique, continuous role in HSC development from generation through survival.
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