摘要：SummaryThe Wnt/β-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 anin vitrosystem enabling inducible gene expression control, we report that moderate induction of transcriptionally active exogenous β-catenin in β-catenin null mouse ESCs promotes epiblast-like cell (EpiLC) derivationin vitro. Instead, in wild-type cells, moderate chemical pre-activation of the Wnt/β-catenin pathway promotes EpiLCin vitroderivation. Finally, we suggest that moderate β-catenin levels in β-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 β-catenin in pluripotency and differentiation, while indicating a role for its doses in promoting specific differentiation programs.Graphical abstractDisplay OmittedHighlights•Moderate β-catenin levels promote EpiLCs derivationin vitro•Chemical pre-activation of the Wnt pathway enhances ESC-EpiLC transition•β-catenin overexpression tips the balance between mesoderm and endoderm•Cell fate is influenced by the extent of β-catenin inductionCell biology; Stem cells research
