广州国家实验室José C.R. Silva研究小组取得一项新突破。他们揭示了通过化学诱导胚胎建立细胞实现器官发生的小鼠胚胎发生的完整模型。这一研究成果发表在2025年8月7日出版的国际学术期刊《细胞》上。
研究人员采用仅小分子的方法将无主题胚胎干细胞诱导成8-16个细胞样的胚胎建立细胞，从而能够生成完整的胚胎模型。这些创始细胞指定所有囊胚谱系，包括胚胎和胚胎外，体内和体外。仅由胚胎创始细胞制成的胚胎模型忠实地再现了器官发生的发育过程。在原肠胚形成过程中，原肠胚通过上皮细胞向间充质细胞的转变形成一条原始条纹，产生三个胚层，并发育出胎盘外锥体。模型继续形成6-14对体、前/中/后脑、一个环心管、视芽、尿囊、尾芽、迁移的原始生殖细胞和明确的肠道。总之，他们的系统主题胚胎创始细胞实现了一个直接，快速，高效，准确的体外胚胎发生模型。
据了解，胚胎模型为理解发育和推进医学提供了机会，但依赖于复杂的程序，在效率和发育保真度方面存在局限性。
附：英文原文
Title: A complete model of mouse embryogenesis through organogenesis enabled by chemically induced embryo founder cells
Author: Huanhuan Li, Wei Guan, Jiahui Huang, Penglei Shen, Jinyi Wu, Haiping Luo, Yun Yang, Shaoqiang Ning, Litao Chang, Haiyong Zhao, Chuanxin Chen, Yake Gao, Yaoyu Chen, Xianfa Yang, Yael Costa, Chen-Leng Cai, Duanqing Pei, Guangdun Peng, Guangming Wu, Jiekai Chen, Jian Zhang, Naihe Jing, José C.R. Silva
Issue&Volume: 2025-08-07
Abstract: Embryo models offer opportunities for understanding development and advancing medicine but rely on intricate procedures with limitations in efficiency and developmental fidelity. Here, we employ a small-molecule-only approach to induce mouse embryonic stem cells into 8- to 16-cell-like embryo founder cells, enabling the generation of a complete embryo model. These founder cells specify all blastocyst lineages, both embryonic and extraembryonic, in vivo and in vitro. The embryo model made only from embryo founder cells faithfully recapitulates development through organogenesis. During gastrulation, it forms a primitive streak via epithelial-to-mesenchymal transition, generates the three germ layers, and develops an ectoplacental cone. The model proceeds to form 6–14 somite pairs, fore-/mid-/hindbrain, a looping heart tube, optic buds, allantois, tail bud, migrating primordial germ cells, and well-defined gut. Altogether, our system using embryo founder cells enables a direct, rapid, efficient, and accurate in vitro model of embryogenesis.
DOI: 10.1016/j.cell.2025.07.018
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00807-4