2025年 新着論文 43 発生生物学分野から論文が発表されました

p53-mediated regulation of epiblast cell numbers predicts reactivation during mouse embryonic diapause

Cell Rep. 2025 Sep 17;44(10):116298. doi: 10.1016/j.celrep.2025.116298. Online ahead of print.

Authors

Affiliations

  • 1 Institute of Advanced Medical Sciences, Tokushima University, Kuramoto, Tokushima, Japan.
  • 2 Department of Multi-Omics, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan; Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
  • 3 Department of Computational and Systems Biology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan; Laboratory of Computational Life Science, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
  • 4 Department of Computational and Systems Biology, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan.
  • 5 Division of Transcriptomics, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
  • 6 Institute of Advanced Medical Sciences, Tokushima University, Kuramoto, Tokushima, Japan; Institute of Photonics and Human Health Frontier, Tokushima University, Kuramoto, Tokushima, Japan.
  • 7 Institute of Advanced Medical Sciences, Tokushima University, Kuramoto, Tokushima, Japan; Institute of Photonics and Human Health Frontier, Tokushima University, Kuramoto, Tokushima, Japan; PRESTO, Japan Science and Technology Agency, Kawaguchi, Saitama, Japan. Electronic address: takaoka.katsuyoshi@tokushima-u.ac.jp.

Abstract

Embryonic diapause is a temporary suspension of proliferation in mammalian pre-implantation embryos, allowing for reactivation later. Cells in mouse diapause embryos enter the G0 phase within 7 days of diapause initiation. Here, we show that approximately 5% of cells in embryonic tissues continue to proliferate even after 7 days of diapause. Transcriptome and phenotypic analyses reveal that p53 facilitated DNA damage repair via p21-mediated cell cycle arrest and regulated epiblast cell numbers via Bax-mediated apoptosis. Moreover, epiblast cell numbers strongly correlated with reactivation rates, with deviations from optimal levels impairing successful reactivation. Our findings call into question the conventional view that all cells in diapause embryos uniformly enter G0. We established epiblast characteristics as predictive factors for determining reactivation success, the defining event of diapause.

Keywords: CP: Developmental biology; G0 stage; apoptosis; blastocyst; cell differentiation; cell proliferation; embryonic diapause; implantation.

Conflict of interest statement

Declaration of interests The authors declare that they have no competing interests.