Mouse sustained epiblast-like cells established by Wnt/beta-catenin signaling manifest distinct features of formative pluripotency. Mus musculus

Formative pluripotent stem cells are recently established in vitro harboring unique functional properties of lineage neutral and germline competence. However, these different stem cell lines are distinct molecular entities regarding formative pluripotency. Here, we showed that canonical WNT signaling can sustain and propagate transient mouse epiblast-like cells, designated as sEpiLCs. sEpiLCs display cellular energy metabolism, transcriptomic features and chromatin accessibility landscape of naive to primed pluripotency transition. sEpiLCs uniquely recapitulate a developmental period in vivo and span the gap of formative pluripotency continuum between other cell lines. Canonical WNT signaling counteracted priming effects by Activin A and FGF2 through sustaining cycling of two early cell states. In addition, sEpiLCs have direct competence for the germline specification, which is further matured by PD. Our sEpiLCs can serve as a unique in vitro model for mimicking and studying early post-implantation development and pluripotency transition.