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

First Author  Ishiuchi T Year  2019
Journal  Cell Rep Volume  27
Issue  6 Pages  1742-1754.e6
PubMed ID  31067460 Mgi Jnum  J:289834
Mgi Id  MGI:6431999 Doi  10.1016/j.celrep.2019.04.028
Citation  Ishiuchi T, et al. (2019) Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development. Cell Rep 27(6):1742-1754.e6
abstractText  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.
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