Decoding primitive endoderm - epiblast interactions using mouse ICM embryoids

Stem cell-based embryo models are promising alternatives for investigating early embryogenesis. We introduce two distinct models to replicate the dynamics between extra-embryonic endoderm and epiblast during mouse embryonic development. Inducible Gata6 (i Gata6 ) embryoid bodies (EBs), exclusively derived from i Gata6 embryonic stem (ES) cells, are valuable for modeling the position-dependent development of the primitive endoderm. Inner cell mass (ICM) embryoids, conversely, efficiently formed by aggregating ‘wild-type’ and i Gata6 ES cells, accurately and at a comparable pace simulate in vivo development from E3.5 to E7.5. Notably, ICM embryoids model cell sorting and through a rosette-like stage, the transition of the epiblast from naïve to primed pluripotency. Furthermore, the absence of extra-embryonic ectoderm-like cells in this model, directs both the epiblast and visceral endoderm towards an anterior developmental fate. As such, i Gata6 EBs and ICM embryoids are powerful tools for advancing our understanding of cell fate decisions during early embryonic development in mice.