Postdoc Guangzhou National Laboratory Guangzhou, Guangdong, China
Abstract: Embryo models open exciting opportunities for improving our understanding of development and advancing medicine. However, current models depend on intricate procedures and the integration of separately generated cell types. Here, we established a chemical-only strategy to induce cellular plasticity and generate embryo founder cells (EFCs) with full developmental potential both in vivo and in vitro solely from embryonic stem cells (ESCs). Within 60 hours, chemical-induced pluripotent stem cells activated the co-expression of early lineage specifiers: Cdx2, Gata6 and Oct4/Pou5f1, acquiring the 8-16-cell characteristics. In vivo, the EFCs have high and balanced contribution (>50%) to both embryonic and extraembryonic tissues in the chimeric assay. In vitro, the EFCs specified into three blastocyst fates and self-assembled into embryo-like structures, term ci-MOs (chemically induced embryo model). Then, 85% of the ci-MOs progressed into high-fidelity late-streak gastrulation stages (E7.5) within 4.5 days, displaying primitive streak formation via epithelial-to-mesenchymal transition, along with germ-layer tissues, amnion, and ectoplacental cone. More than 36% of the gastrulating ci-MOs further developed into organogenesis stages containing high degree of morphology similarity with natural E8.5-E9.0 embryos, containing looping heart tube, 5-7 somite-pairs, prominent neural fold, anterior neuropore formation, clear foregut, and hindgut pocket, etc. Fate trajectories and molecular signatures from ci-EFCs to ci-MOs revealed remarkable similarity to natural development from E2.5 to E8.5~9.0 embryo. Summarily, ci-EFCs efficiently and accurately mimic embryo development, offering a game-changer, straightforward, rapid, small-molecule-only, and high-fidelity approach to study cell fate specification and model embryonic development from preimplantation to organogenesis.
