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  3. A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation

A continuous totipotent-like cell-based embryo model recapitulates mouse embryogenesis from zygotic genome activation to gastrulation

  • Nat Cell Biol. 2025 Oct 15. doi: 10.1038/s41556-025-01793-9.
Yixuan Ren # 1 2,  Xuyang Wang # 3,  Haiyin Liu # 3,  Yaxing Xu # 4,  Ruoqi Cheng # 5,  Shengnan Ren # 6,  Zining Li 1,  Yunfei Huo 1,  Bo Li 1,  Jingyang Guan 7,  Cheng Li 8,  Hongkui Deng 9 10,  Jun Xu 11
Affiliations

Affiliations

  • 1 MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
  • 3 Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Peking University, Beijing, China.
  • 4 Department of Biochemistry and Molecular Biology, College of Basic Medicine, Key Laboratory of Neural and Vascular Biology of Ministry of Education, Key Laboratory of Vascular Biology of Hebei Province, Hebei Medical University, Shijiazhuang, China.
  • 5 School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China.
  • 6 State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
  • 7 State Key Laboratory of Natural and Biomimetic Drugs, Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China. guanjingyang@hsc.pku.edu.cn.
  • 8 School of Life Sciences, Center for Bioinformatics, Center for Statistical Science, Peking University, Beijing, China. cheng_li@pku.edu.cn.
  • 9 MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences and MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. hongkui_deng@pku.edu.cn.
  • 10 Changping Laboratory, Beijing, China. hongkui_deng@pku.edu.cn.
  • 11 Department of Cell Biology, School of Basic Medical Sciences, Peking University Stem Cell Research Center, Peking University Health Science Center, Peking University, Beijing, China. jun_xu@bjmu.edu.cn.
  • # Contributed equally.
PMID: 41094030 DOI: 10.1038/s41556-025-01793-9
Abstract

The development of stem-cell-derived models of mammalian embryogenesis has provided invaluable tools for investigating embryo development. However, constructing embryo models that can continuously recapitulate the developmental trajectory, from zygotic genome activation to gastrulation, remains challenging. Here we report the development of a chemical cocktail to induce totipotent-like cells with robust proliferative ability and leverage these cells to establish a stepwise protocol for generating a continuous embryo model. This model sequentially mimics mouse embryogenesis from embryonic day 1.5 to 7.5. It recapitulates key developmental milestones, including zygotic genome activation in 2-cell embryos, the diversification of embryonic and extraembryonic lineages from 4-cell to 64-cell stages, the formation of blastocysts and the subsequent development into post-implantation egg cylinders. Notably, these structures undergo gastrulation, as indicated by the formation of a primitive streak-like structure and the subsequent emergence of several early organogenesis hallmarks. Our study opens avenues for modelling mammalian embryogenesis in vitro.

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