LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2
| Autor: | Mana Watanabe, Yuji Fuse, Makoto Kobayashi, Christina-Sylvia Andrea, Maki Kobayashi-Osaki, Miki Takeuchi, Ken Ohashi, Miho Takeuchi, Hiroshi Kaneko, Masayuki Yamamoto, Hitomi Nakajima |
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| Rok vydání: | 2015 |
| Předmět: |
animal structures
Hemangioblasts Cellular differentiation Molecular Sequence Data Down-Regulation Biology Vasculogenesis Animals Cell Lineage Progenitor cell Zebrafish Regulation of gene expression Histone Demethylases Gene knockdown Multidisciplinary KDM1A Zebrafish Proteins Biological Sciences biology.organism_classification Molecular biology Cell biology Hematopoiesis Up-Regulation Gene Knockdown Techniques Mutation Hemangioblast |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 112(45) |
| ISSN: | 1091-6490 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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