β-catenin perturbations control differentiation programs in mouse embryonic stem cells
β-catenin perturbations control differentiation programs in mouse embryonic stem cells
Abstract 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, we applied an elegant in vitro system enabling conditional β-catenin control in β-catenin null mouse ESCs. We report that moderate induction of transcriptionally active exogenous β-catenin enhances epiblast-like cell (EpiLC) derivation in vitro. Using a different genetic model and β-catenin chemical modulation, we found that pre-activation of the Wnt/β-catenin pathway enhances EpiLC in vitro derivation. Finally, we suggest that moderate β-catenin levels favour early stem cell commitment towards mesoderm if the protein is overexpressed only in the ‘ground state’ of pluripotency condition, or endoderm if the overexpression 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.
Marucci Lucia、Pedone Elisa、Gambardella Gennaro、Failli Mario、di Bernardo Diego、De Cegli Rossella
Department of Engineering Mathematics, University of Bristol||School of Cellular and Molecular Medicine, University of Bristol||BrisSynBioDepartment of Engineering Mathematics, University of Bristol||School of Cellular and Molecular Medicine, University of BristolTelethon Institute of Genetic and Medicine Via Campi Flegrei 34||Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico IITelethon Institute of Genetic and Medicine Via Campi Flegrei 34||Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico IITelethon Institute of Genetic and Medicine Via Campi Flegrei 34||Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico IITelethon Institute of Genetic and Medicine Via Campi Flegrei 34
分子生物学细胞生物学遗传学
Marucci Lucia,Pedone Elisa,Gambardella Gennaro,Failli Mario,di Bernardo Diego,De Cegli Rossella.β-catenin perturbations control differentiation programs in mouse embryonic stem cells[EB/OL].(2025-03-28)[2025-06-09].https://www.biorxiv.org/content/10.1101/2020.05.15.098137.点此复制
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