北京大学徐君小组宣布他们研制了基于连续类全能性细胞的胚胎模型再现小鼠从合子基因组激活到原肠胚形成的发育过程。相关论文发表在2025年10月15日出版的《自然—细胞生物学》杂志上。

在这里，研究小组报告了一种化学混合物的发展，以诱导具有机器人增殖能力的全能样细胞，并利用这些细胞建立一个逐步产生连续胚胎模型的方案。该模型从胚胎第1.5天到第7.5天依次模拟无母胚发生。它概述了关键的发育里程碑，包括2细胞胚胎的合子基因组激活，胚胎和胚胎外谱系从4细胞到64细胞阶段的多样化，囊胚的形成以及随后的植入后卵柱的发育。值得注意的是，这些结构经历了原肠胚形成，如原始条纹状结构的形成和随后出现的几个早期器官发生标志所示。他们的研究为在体外模拟哺乳动物胚胎发生开辟了道路。

研究人员表示，哺乳动物胚胎发生的干细胞衍生模型的发展为研究胚胎发育提供了宝贵的工具。然而，构建能够连续再现从合子基因组激活到原肠胚形成的发育轨迹的胚胎模型仍然具有挑战性。

附：英文原文

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

Author: Ren, Yixuan, Wang, Xuyang, Liu, Haiyin, Xu, Yaxing, Cheng, Ruoqi, Ren, Shengnan, Li, Zining, Huo, Yunfei, Li, Bo, Guan, Jingyang, Li, Cheng, Deng, Hongkui, Xu, Jun

Issue&Volume: 2025-10-15

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.

DOI: 10.1038/s41556-025-01793-9

Source: https://www.nature.com/articles/s41556-025-01793-9