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Proc Natl Acad Sci U S A. 2015 Nov 10;112(45):13922-7. doi: 10.1073/pnas.1517326112. Epub 2015 Oct 28.

LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2.

Author information

1
Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan;
2
Exploratory Research for Advanced Technology Environmental Response Project, Japan Science and Technology Agency, University of Tsukuba, Tsukuba 305-8575, Japan;
3
Exploratory Research for Advanced Technology Environmental Response Project, Japan Science and Technology Agency, University of Tsukuba, Tsukuba 305-8575, Japan; Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
4
Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; Exploratory Research for Advanced Technology Environmental Response Project, Japan Science and Technology Agency, University of Tsukuba, Tsukuba 305-8575, Japan; makobayash@md.tsukuba.ac.jp.

Abstract

The hemangioblast is a progenitor cell with the capacity to give rise to both hematopoietic and endothelial progenitors. Currently, the regulatory mechanisms underlying hemangioblast formation are being elucidated, whereas those controllers for the selection of hematopoietic or endothelial fates still remain a mystery. To answer these questions, we screened for zebrafish mutants that have defects in the hemangioblast expression of Gata1, which is never expressed in endothelial progenitors. One of the isolated mutants, it627, showed not only down-regulation of hematopoietic genes but also up-regulation of endothelial genes. We identified the gene responsible for the it627 mutant as the zebrafish homolog of Lys-specific demethylase 1 (LSD1/KDM1A). Surprisingly, the hematopoietic defects in lsd1(it627) embryos were rescued by the gene knockdown of the Ets variant 2 gene (etv2), an essential regulator for vasculogenesis. Our results suggest that the LSD1-dependent shutdown of Etv2 gene expression may be a significant event required for hemangioblasts to initiate hematopoietic differentiation.

KEYWORDS:

Gata1; cell differentiation; gene regulation; histone demethylase; zebrafish

PMID:
26512114
PMCID:
PMC4653156
DOI:
10.1073/pnas.1517326112
[Indexed for MEDLINE]
Free PMC Article

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