β-catenin perturbations control differentiation programs in mouse embryonic stem cells

The Wnt/beta-catenin pathway is involved in development, cancer, and embryonic stem cell (ESC) maintenance; its dual role in stem cell self-renewal and differentiation is still controversial. Here, by applying an in vitro system enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous beta-catenin in beta-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivation in vitro. Instead, in wild-type cells, moderate chemical pre-activation of the Wnt/beta-catenin pathway promotes EpiLC in vitro derivation. Finally, we suggest that moderate beta-catenin levels in beta-catenin null mouse ESCs favor early stem cell commitment toward mesoderm if the exogenous protein is induced only in the "ground state"of pluripotency condition, or endoderm if the induction is maintained during the differentiation. Overall, our results confirm previous findings about the role of beta-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs.