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Domain‐specific biological functions of the transcription factor Gata2 on hematopoietic differentiation of mouse embryonic stem cells
Author(s) -
Kitajima Kenji,
Kanokoda Mai,
Nakajima Marino,
Hara Takahiko
Publication year - 2018
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12628
Subject(s) - gata2 , biology , embryonic stem cell , haematopoiesis , microbiology and biotechnology , transcription factor , stem cell , gata transcription factor , cellular differentiation , gata1 , genetics , gene expression , gene , promoter
Abstract The generation of mouse hematopoietic stem cells from hemogenic endothelial cells ( HEC s) in the aorta/gonad/mesonephros region of developing embryos requires a zinc finger transcription factor Gata2 . In the previous study, an enforced expression of Gata2 in vitro promoted the production of HEC s from mesodermal cells differentiated from mouse embryonic stem cells ( ESC s). Our research group has previously demonstrated that the enforced expression of Gata2 in ESC ‐derived HEC s enhances erythroid and megakaryocyte differentiation and inhibits macrophage differentiation. However, the manner in which the multiple functions of Gata2 are regulated remains unclear. Mouse ESC s differentiate into various types of hematopoietic cells when cocultured with OP 9 stromal cells ( OP 9 system). Using this system and the inducible gene cassette exchange system, which facilitates the establishment of ESC s carrying inducible transgenes under an identical gene expression regulatory unit, the domain‐specific functions of Gata2 were systematically dissected in this study. We determined that the N‐terminal (amino acid 1–110) region of Gata2 was an erythroid‐inducing region, both the middle (amino acid 111–200) and C‐terminal (amino acid 413–480) regions were megakaryocyte‐inducing regions. Furthermore, the present data strongly suggest that intramolecular antagonistic interactions between each of these regions fine‐tune the biological functions of Gata2.