Chemically induced cell plasticity enables the generation of High-fidelity embryo model (PRJCA026834)

Embryo models open exciting opportunities for improving our understanding of development and advancing medicine. However, these rely on a mixture of three cell types rather than a single founder cell source. Here, we aimed to establish a chemical-only strategy to induce cellular plasticity and generate embryo founder-like cells. Within 60 hours, chemically-induced pluripotent stem cells activated early lineage specifiers, Cdx2 and Gata6, while maintaining Oct4 expression. Following a second 36-hour chemical treatment, founder-like cells developed into one of the three blastocyst fates and self-assembled into embryo-like structures. These progressed into high-fidelity late-streak gastrulation stages within 4.5 days, displaying correct primitive streak, germ-layer tissues, epithelial-to-mesenchymal transition, allantois, amnion and ectoplacental cone. Fate trajectories and molecular signatures from founder-like cells to chemically-induced embryo models (ciMOs) were defined, revealing remarkable molecular similarity until at least E7.5 embryos. Summarily, ciMO offers a straightforward, rapid, direct, compound-only, and High-fidelity approach for studying embryonic development and cell fate specification.