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

Miki Takeuchi, Yuji Fuse, Mana Watanabe, Christina Sylvia Andrea, Miho Takeuchi, Hitomi Nakajima, Ken Ohashi, Hiroshi Kaneko, Maki Kobayashi-Osaki, Masayuki Yamamoto, Makoto Kobayashi

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16 Citations (Scopus)

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 lsd1it627 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.

Original languageEnglish
Pages (from-to)13922-13927
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number45
DOIs
Publication statusPublished - 2015 Nov 10

ASJC Scopus subject areas

  • General

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    Takeuchi, M., Fuse, Y., Watanabe, M., Andrea, C. S., Takeuchi, M., Nakajima, H., Ohashi, K., Kaneko, H., Kobayashi-Osaki, M., Yamamoto, M., & Kobayashi, M. (2015). LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2. Proceedings of the National Academy of Sciences of the United States of America, 112(45), 13922-13927. https://doi.org/10.1073/pnas.1517326112