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

doi:10.1016/j.isci.2022.103756

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 journal › Article (Academic Journal) › peer-review

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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 language	English
Article number	103756
Number of pages	22
Journal	iScience
Volume	25
Issue number	2
Early online date	27 Jan 2022
DOIs	https://doi.org/10.1016/j.isci.2022.103756
Publication status	Published - 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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10.1016/j.isci.2022.103756Licence: CC BY

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β-catenin perturbations control differentiation programs in mouse embryonic stem cells
Pedone, E., Failli, M., Gambardella, G., De Cegli, R., La Regina, A., di Bernardo, D. & Marucci, L., 18 Feb 2022, In: iScience. 25, 2, 22 p., 103756.
Research output: Contribution to journal › Article (Academic Journal) › peer-review

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1 Active

COMBO: CONTROL-BASED BIODESIGN OF MAMMALIAN CELL DYNAMICS
Marucci, L.
1/10/19 → 30/09/24
Project: Research
Unravelling the role of beta-catenin in ground state pluripotency
Marucci, L.
1/09/16 → 31/08/19
Project: Research, Parent

Cite this

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title = "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, 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.",

author = "Elisa Pedone and Mario Failli and Gennaro Gambardella and {De Cegli}, Rossella and {La Regina}, Antonella and {di Bernardo}, Diego and Lucia Marucci",

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: {\textcopyright} 2022 The Authors",

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AU - Pedone, Elisa

AU - Failli, Mario

AU - Gambardella, Gennaro

AU - De Cegli, Rossella

AU - La Regina, Antonella

AU - di Bernardo, Diego

AU - Marucci, Lucia

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DO - 10.1016/j.isci.2022.103756

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JF - iScience

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IS - 2

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

Abstract

Bibliographical note

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Research output

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

Projects

COMBO: CONTROL-BASED BIODESIGN OF MAMMALIAN CELL DYNAMICS

Unravelling the role of beta-catenin in ground state pluripotency

Cite this