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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Ishiuchi T,Ohishi H,Sato T,Kamimura S,Yorino M,Abe S,Suzuki A,Wakayama T,Suyama M,Sasaki Hdoi
10.1016/j.celrep.2019.04.028subject
Has Abstractpub_date
2019-05-07 00:00:00pages
1742-1754.e6issue
6issn
2211-1247pii
S2211-1247(19)30493-0journal_volume
27pub_type
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