Stem cell-derived mouse embryos develop within an extra-embryonic yolk sac to form anterior brain regions and a beating heart

We report the analysis by inDrop single cell sequencing of mouse embryos at embryonic day E6.5, E7.5 and E8.5 as well as the analysis of stem cell derived synthetic embryos generated with the previously reported protocol (Amadei et al., 2021) and cultured to day 5, day 6 and day 8 of development. We find that all the cell types present in the natural embryos examined at these timepoints were also present in their synthetic counterparts. Furthermore, in these synthetic structures we observed formation of neuroectoderm and surface ectoderm, a beating heart, gut and primordial germ cells and development occurred inside extraembryonic membranes (yolk sac and amnion) similarly to what occurs in natural development. We conclude that these synthetic embryos are a unique tool to recapitulate mouse post-implantation development. Overall design: Analysis of similarities and differences in the transcriptomes among mouse embryos and stem cell derived synthetic embryos, generated with the recently reported protocol (Amadei et al., 2021) and the new protocol established in this study