β-catenin perturbations control differentiation programs in mouse embryonic stem cells
Elisa Pedone,
Mario Failli,
Gennaro Gambardella,
Rossella De Cegli,
Antonella La Regina,
Diego di Bernardo,
Lucia Marucci
Affiliations
Elisa Pedone
Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK; School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; Corresponding author
Mario Failli
Telethon Institute of Genetic and Medicine Via Campi Flegrei34, 80078 Pozzuoli, Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy
Gennaro Gambardella
Telethon Institute of Genetic and Medicine Via Campi Flegrei34, 80078 Pozzuoli, Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy
Rossella De Cegli
Telethon Institute of Genetic and Medicine Via Campi Flegrei34, 80078 Pozzuoli, Italy
Antonella La Regina
Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK; School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; Department of Electrical Engineering and Information Technology, University of Naples Federico II, 80125 Naples, Italy
Diego di Bernardo
Telethon Institute of Genetic and Medicine Via Campi Flegrei34, 80078 Pozzuoli, Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy
Lucia Marucci
Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK; School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK; BrisSynBio, Bristol BS8 1TQ, UK; Corresponding author
Summary: The 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 an in vitro system 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) derivation in vitro. Instead, in wild-type cells, moderate chemical pre-activation of the Wnt/β-catenin pathway promotes EpiLC in vitro derivation. 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.
