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*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
67 Downloads (Pure)

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, 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.
Original languageEnglish
Article number103756
Number of pages22
JournaliScience
Volume25
Issue number2
Early online date27 Jan 2022
DOIs
Publication statusPublished - 18 Feb 2022

Bibliographical note

Funding Information:
We thank Dr Andre Hermann and Dr Lorena Sueiro Ballesteros (Flow Cytometry Facility, University of Bristol), Dr Mark Jepson and Alan Leard (Wolfson Imaging Facility, University of Bristol) and the Next Generation Sequencing Core (TIGEM, Naples) for their support. This work was funded by Medical Research Council (grant MR/N021444/1) to L.M. by the Engineering and Physical Sciences Research Council (grants EP/R041695/1 and EP/S01876X/1 to L.M.), EC funding H2020 (FET OPEN 766840-COSY-BIO) to L.M. BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre (BB/L01386X/1) to L.M. STAR-University of Naples Federico II grant to G.G. and Fondazione Telethon grant to D.d.B. E.P. designed and performed experiments; M.F. and G.G. performed the WGNCA analysis; M.F. performed the GO; R.D.C. performed the Differential Expression analysis; A.L.R. supported the experimental work; E.P. and L.M. analyzed data; E.P. M.F. R.D.C. and L.M. wrote the paper; D.d.B. supervised the bioinformatics analysis; L.M. supervised the entire project. The authors declare that they have no competing interests.

Funding Information:
We thank Dr Andre Hermann and Dr Lorena Sueiro Ballesteros (Flow Cytometry Facility, University of Bristol), Dr Mark Jepson and Alan Leard (Wolfson Imaging Facility, University of Bristol) and the Next Generation Sequencing Core (TIGEM, Naples) for their support. This work was funded by Medical Research Council (grant MR/N021444/1 ) to L.M., by the Engineering and Physical Sciences Research Council (grants EP/R041695/1 and EP/S01876X/1 to L.M.), EC funding H2020 (FET OPEN 766840-COSY-BIO) to L.M., BrisSynBio, a BBSRC / EPSRC Synthetic Biology Research Centre ( BB/L01386X/1 ) to L.M., STAR- University of Naples Federico II grant to G.G., and Fondazione Telethon grant to D.d.B.

Publisher Copyright:
© 2022 The Authors

Structured keywords

  • Mathematics and Computational Biology
  • Engineering Mathematics Research Group

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