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Cell Rep. 2019 May 7;27(6):1742-1754.e6. doi: 10.1016/j.celrep.2019.04.028.

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

Author information

1
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: ishiuchi@bioreg.kyushu-u.ac.jp.
2
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
3
Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
4
Advanced Biotechnology Center, University of Yamanashi, Yamanashi 400-8510, Japan.
5
Division of Organogenesis and Regeneration, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
6
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: hsasaki@bioreg.kyushu-u.ac.jp.

Abstract

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.

KEYWORDS:

MLL-COMPASS; Zfp281; placental development; trophoblast stem cell

PMID:
31067460
DOI:
10.1016/j.celrep.2019.04.028
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