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

iScience

Gennaro Gambardella¹  Antonella La Regina²  Lucia Marucci²  Mario Failli³  Elisa Pedone⁴  Rossella De Cegli⁵  Diego di Bernardo⁵ 

[1] Corresponding author;Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, 80125 Naples, Italy;School of Cellular and Molecular Medicine, University of Bristol, Bristol BS8 1TD, UK;Department of Engineering Mathematics, University of Bristol, Bristol BS8 1UB, UK;Telethon Institute of Genetic and Medicine Via Campi Flegrei34, 80078 Pozzuoli, Italy;

关键词: Cell biology;    Stem cells research;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown