Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1

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• dc.contributor.author Aulicino, Francesco, 1987-
• dc.contributor.author Theka, Ilda, 1984-
• dc.contributor.author Ombrato, Luigi
• dc.contributor.author Lluis Vinas, Frederic
• dc.contributor.author Cosma, Maria Pia
• dc.date.accessioned 2023-06-26T06:03:31Z
• dc.date.available 2023-06-26T06:03:31Z
• dc.date.issued 2014
• dc.description Includes supplementary materials for the online appendix.
• dc.description.abstract Cyclic activation of the Wnt/β-catenin signaling pathway controls cell fusion-mediated somatic cell reprogramming. TCFs belong to a family of transcription factors that, in complex with β-catenin, bind and transcriptionally regulate Wnt target genes. Here, we show that Wnt/β-catenin signaling needs to be off during the early reprogramming phases of mouse embryonic fibroblasts (MEFs) into iPSCs. In MEFs undergoing reprogramming, senescence genes are repressed and mesenchymal-to-epithelial transition is favored. This is correlated with a repressive activity of TCF1, which contributes to the silencing of Wnt/β-catenin signaling at the onset of reprogramming. In contrast, the Wnt pathway needs to be active in the late reprogramming phases to achieve successful reprogramming. In conclusion, continued activation or inhibition of the Wnt/β-catenin signaling pathway is detrimental to the reprogramming of MEFs; instead, temporal perturbation of the pathway is essential for efficient reprogramming, and the “Wnt-off” state can be considered an early reprogramming marker.
• dc.description.sponsorship We would like to thank Karthik Arumugam, Lucia Marucci, and Elisa Pedone for critically reading the manuscript; Bruno Di Stefano for suggestions to iPSC generation experiments; and Vanessa Chigancas and Neus Romo for technical support. We thank Luigi Naldini for providing lentiviral vectors, Hans Clevers for providing the Tcf1 constructs, and Rudolf Jaenisch for providing the inducible four-factor mouse model. We are grateful for support from an European Research Council grant (242630-RERE) (to M.P.C.), an HFSP grant (to M.P.C.), the Ministerio de Ciencia e Inovación (SAF2011-28580) (to M.P.C.), Fundacio’ La Marato’ de TV3 (to M.P.C.), the AXA Research Fund (to M.P.C.), the “Miguel Servet” Project of the Instituto de Salud Carlos III (CP10/00445) (to F.L.), the Ministerio de Ciencia e Innovación FPI (to F.A.), and the Ingenium ITN Marie Curie Program (to I.T.). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013-2017” (SEV-2012-0208).
• dc.format.mimetype application/pdf
• dc.identifier.citation Aulicino F, Theka I, Ombrato L, Lluis F, Pia M. Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1. Stem Cell Reports. 2014 May 6;2(5):707-20. DOI: 10.1016/j.stemcr.2014.04.001
• dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2014.04.001
• dc.identifier.issn 2213-6711
• dc.identifier.uri http://hdl.handle.net/10230/57338
• dc.language.iso eng
• dc.publisher Cell Press
• dc.relation.ispartof Stem Cell Reports. 2014 May 6;2(5):707-20
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/242630
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2011-28580
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SEV-2012-0208
• dc.rights This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
• dc.subject.other Cèl·lules mare
• dc.subject.other Cèl·lules mare embrionàries
• dc.subject.other Genètica animal
• dc.title Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion