A complete model of mouse embryogenesis through organogenesis enabled by chemically induced embryo founder cells
Huanhuan Li, Wei Guan, Jiahui Huang, Penglei Shen, Jinyi Wu, Haiping Luo, Yunsheng 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 Silva
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.