Li Huanhuan, Guan Wei, Huang Jiahui, Shen Penglei, Wu Jinyi, Luo Haiping, Yang Yun, Ning Shaoqiang, Chang Litao, Zhao Haiyong, Chen Chuanxin, Gao Yake, Chen Yaoyu, Yang Xianfa, Costa Yael, Cai Chen-Leng, Pei Duanqing, Peng Guangdun, Wu Guangming, Chen Jiekai, Zhang Jian, Jing Naihe, Silva José C R
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou 510005, China; Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou 510005, Guangdong, China.
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou National Laboratory, Guangzhou Medical University, Guangzhou 510005, China; Guangzhou National Laboratory, Guangzhou International Bio Island, Guangzhou 510005, Guangdong, China.
Cell. 2025 Aug 7. doi: 10.1016/j.cell.2025.07.018.
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.
胚胎模型为理解发育过程和推动医学进步提供了机会，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。在这里，我们采用仅使用小分子的方法将小鼠胚胎干细胞诱导为8至16细胞样胚胎起始细胞，从而能够生成完整的胚胎模型。这些起始细胞在体内和体外均可指定所有囊胚谱系，包括胚胎谱系和胚外谱系。仅由胚胎起始细胞制成的胚胎模型忠实地再现了直至器官发生阶段的发育过程。在原肠胚形成过程中，它通过上皮-间充质转化形成原条，产生三个胚层，并发育出一个外胎盘锥。该模型进而形成6至14对体节、前脑/中脑/后脑、一个环状心管、视芽、尿囊、尾芽、迁移的原始生殖细胞以及明确的肠道。总之，我们使用胚胎起始细胞的系统能够建立直接、快速、高效且准确的体外胚胎发生模型。
