Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development

Takashi Ishiuchi, Hiroaki Ohishi, Tetsuya Sato, Satoshi Kamimura, Masayoshi Yorino, Shusaku Abe, Atsushi Suzuki, Teruhiko Wakayama, Mikita Suyama, Hiroyuki Sasaki

研究成果: Contribution to journalArticle査読

16 被引用数 (Scopus)

抄録

Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying placental development is not fully understood. Here, we conduct a forward genetic screen to identify regulators for extraembryonic development and identify Zfp281 as a key factor. Zfp281 overexpression in mouse embryonic stem cells facilitates the induction of trophoblast stem-like cells. Zfp281 is preferentially expressed in the undifferentiated trophoblast stem cell population in an FGF-dependent manner, and disruption of Zfp281 in mice causes severe defects in early placental development. Consistently, Zfp281-depleted trophoblast stem cells exhibit defects in maintaining the transcriptome and differentiation capacity. Mechanistically, Zfp281 interacts with MLL or COMPASS subunits and occupies the promoters of its target genes. Importantly, ZNF281, the human ortholog of this factor, is required to stabilize the undifferentiated status of human trophoblast stem cells. Thus, we identify Zfp281 as a conserved factor for the maintenance of trophoblast stem cell plasticity. Ishiuchi et al. demonstrate that Zfp281 regulates gene expression through the interaction with MLL or COMPASS in trophoblast stem (TS) cells. Depletion of Zfp281 impairs TS cell plasticity in vitro and in vivo. Knockdown of ZNF281 downregulates a set of genes enriched in undifferentiated human TS cells, including ELF5 and LIN28A.

本文言語英語
ページ(範囲)1742-1754.e6
ジャーナルCell Reports
27
6
DOI
出版ステータス出版済み - 5 7 2019

All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)

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