Postdoc Guangzhou National Laboratory Guangzhou, China (People's Republic)
Abstract: Embryo models play a role as surrogates for unraveling human early development. However, existing models show low efficiency when modelling post-implantation stages. Here, we manage to reprogram human pluripotent stem cells (hPSCs) into early embryo fates in 60-120 hours by recreating signaling environment of the blastocyst stage. Upon aggregation, the reprogrammed hPSCs self-assembly to develop into post-implantation embryo-like structures, containing all embryonic and extraembryonic lineages. These structures are morphologically replica of Carnegie Stage (CS) 5-7 embryos, exhibiting a bilaminar disc-like structure, including epiblast and hypoblast discs, yolk-sac and amniotic cavities, mesenchyme tissue, chorionic cavity, and trophoblast at the correct locations. Immunostaining and single-cell RNA sequencing results at different time points reveal that our model also recapitulates key developmental events, including gastrulation, germ cell specification, chorion development, and primary to secondary yolk sac transition. Collectively, we demonstrate that by modulating key signaling of the early embryo allows us to efficiently generate a high-fidelity model to mimic development up to a gastrulating embryo both morphologically and molecularly. Our findings offer a state-of-the-art strategy for advancing our understanding of post-implantation human embryogenesis.
