Decoding primitive endoderm - epiblast interactions using mouse ICM embryoids

Abstract

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 (iGata6) embryoid bodies (EBs), exclusively derived from iGata6 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 iGata6 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 naive 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, iGata6 EBs and ICM embryoids are powerful tools for advancing our understanding of cell fate decisions during early embryonic development in mice.