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Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions

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dc.contributor.author Aulicino, Francesco, 1987-
dc.contributor.author Pedone, Elisa, 1985-
dc.contributor.author Sottile, Francesco, 1988-
dc.contributor.author Lluis Viñas, Frederic
dc.contributor.author Marucci, Lucia
dc.contributor.author Cosma, Maria Pia
dc.date.accessioned 2020-11-02T06:52:46Z
dc.date.available 2020-11-02T06:52:46Z
dc.date.issued 2020
dc.identifier.citation Aulicino F, Pedone E, Sottile F, Lluis F, Marucci L, Cosma MP. Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions. Stem Cell Reports. 2020; 15(3):646-61. DOI: 10.1016/j.stemcr.2020.07.019
dc.identifier.issn 2213-6711
dc.identifier.uri http://hdl.handle.net/10230/45629
dc.description.abstract The Wnt/β-catenin signaling pathway is a key regulator of embryonic stem cell (ESC) self-renewal and differentiation. Constitutive activation of this pathway has been shown to increase mouse ESC (mESC) self-renewal and pluripotency gene expression. In this study, we generated a novel β-catenin knockout model in mESCs to delete putatively functional N-terminally truncated isoforms observed in previous knockout models. We showed that aberrant N-terminally truncated isoforms are not functional in mESCs. In the generated knockout line, we observed that canonical Wnt signaling is not active, as β-catenin ablation does not alter mESC transcriptional profile in serum/LIF culture conditions. In addition, we observed that Wnt signaling activation represses mESC spontaneous differentiation in a β-catenin-dependent manner. Finally, β-catenin (ΔC) isoforms can rescue β-catenin knockout self-renewal defects in mESCs cultured in serum-free medium and, albeit transcriptionally silent, cooperate with TCF1 and LEF1 to inhibit mESC spontaneous differentiation in a GSK3-dependent manner.
dc.description.sponsorship The authors would like to thank the Genomics Unit at the CRG for assistance with the mRNA-seq (library prep and sequencing), and CRG and the Bristol University flow-cytometry facilities. This work was supported by the European Union's Horizon2020 Research and Innovation Programme (CellViewer No 686637 to M.P.C.), Ministerio de Ciencia e Innovación, grant BFU2017-86760-P (AEI/FEDER, UE), and an AGAUR grant from Secretaria d’Universitats i Recerca del Departament d’Empresa I Coneixement de la Generalitat de Catalunya (2017 SGR 689 to M.P.C.).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Stem Cell Reports. 2020; 15(3):646-61
dc.rights © 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Canonical Wnt pathway controls mESC self-renewal through inhibition of spontaneous differentiation via β-catenin/TCF/LEF functions
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2020.07.019
dc.subject.keyword CRISPR
dc.subject.keyword Ctnnb1
dc.subject.keyword LEF
dc.subject.keyword TCF
dc.subject.keyword Wnt
dc.subject.keyword Embryonic stem cells
dc.subject.keyword mESCs
dc.subject.keyword Pluripotency
dc.subject.keyword Self-renewal
dc.subject.keyword β-catenin
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/686637
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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