TY - JOUR
T1 - Zfp281 Shapes the Transcriptome of Trophoblast Stem Cells and Is Essential for Placental Development
AU - Ishiuchi, Takashi
AU - Ohishi, Hiroaki
AU - Sato, Tetsuya
AU - Kamimura, Satoshi
AU - Yorino, Masayoshi
AU - Abe, Shusaku
AU - Suzuki, Atsushi
AU - Wakayama, Teruhiko
AU - Suyama, Mikita
AU - Sasaki, Hiroyuki
N1 - Funding Information:
We thank Wellcome Trust Sanger Institute for piggyBac plasmids, Toru Nakano and Yasuyoshi Kimura for haploid ESC lines and plasmids, Yasuhide Ohinata for TS cell lines and advice, Yasuyuki Ohkawa for helpful discussion, Shinya Oki for help in embryo dissection, Ana Bošković for critical reading of the manuscript, and Hiroaki Okae and Takahiro Arima for human TS cell lines. We also thank the members of our laboratory and common research facilities in Medical Institute of Bioregulation in Kyushu University for technical assistance. This work was supported by grants from JSPS Grant-in-Aid for Young Scientists grant number JP18K14717 , Takeda Science Foundation and Kishimoto Foundation to T.I., and by AMED grant number JP17gm0510011 to H.S. T.I. was a recipient of Human Frontier Science Program long-term fellowship ( LT000015/2012-L ).
Funding Information:
We thank Wellcome Trust Sanger Institute for piggyBac plasmids, Toru Nakano and Yasuyoshi Kimura for haploid ESC lines and plasmids, Yasuhide Ohinata for TS cell lines and advice, Yasuyuki Ohkawa for helpful discussion, Shinya Oki for help in embryo dissection, Ana Bo?kovi? for critical reading of the manuscript, and Hiroaki Okae and Takahiro Arima for human TS cell lines. We also thank the members of our laboratory and common research facilities in Medical Institute of Bioregulation in Kyushu University for technical assistance. This work was supported by grants from JSPS Grant-in-Aid for Young Scientists grant number JP18K14717, Takeda Science Foundation and Kishimoto Foundation to T.I. and by AMED grant number JP17gm0510011 to H.S. T.I. was a recipient of Human Frontier Science Program long-term fellowship (LT000015/2012-L). Conceptualization, T.I.; Investigation, T.I. H.O. S.K. M.Y. S.A. and T.W.; Formal Analysis, T.I. H.O. and T.S.; Writing ? Original Draft, T.I.; Writing ? Review & Editing, T.I. T.S. and H.S.; Supervision, T.I. H.S. M.S. A.S. and T.W.; Funding Acquisition, T.I. and H.S. The authors declare no competing interests.
Publisher Copyright:
© 2019 The Authors
PY - 2019/5/7
Y1 - 2019/5/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2019.04.028
DO - 10.1016/j.celrep.2019.04.028
M3 - Article
C2 - 31067460
AN - SCOPUS:85064894054
SN - 2211-1247
VL - 27
SP - 1742-1754.e6
JO - Cell Reports
JF - Cell Reports
IS - 6
ER -