Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells

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dc.contributor.authorTheka, Ilda, 1984-
dc.contributor.authorSottile, Francesco, 1988-
dc.contributor.authorCammisa, Marco
dc.contributor.authorBonnin, Sarah
dc.contributor.authorSanchez-Delgado, Marta
dc.contributor.authorDi Vicino, Umberto
dc.contributor.authorNeguembor, Maria Victoria
dc.contributor.authorArumugam, Karthik
dc.contributor.authorAulicino, Francesco, 1987-
dc.contributor.authorMonk, David
dc.contributor.authorRiccio, Andrea
dc.contributor.authorCosma, Maria Pia, 1970-
dc.date.accessioned2019-03-22T08:07:20Z
dc.date.available2019-03-22T08:07:20Z
dc.date.issued2019
dc.description.abstractMouse embryonic stem cells (mESCs) are pluripotent and can differentiate into cells belonging to the three germ layers of the embryo. However, mESC pluripotency and genome stability can be compromised in prolonged in vitro culture conditions. Several factors control mESC pluripotency, including Wnt/β-catenin signaling pathway, which is essential for mESC differentiation and proliferation. Here we show that the activity of the Wnt/β-catenin signaling pathway safeguards normal DNA methylation of mESCs. The activity of the pathway is progressively silenced during passages in culture and this results into a loss of the DNA methylation at many imprinting control regions (ICRs), loss of recruitment of chromatin repressors, and activation of retrotransposons, resulting into impaired mESC differentiation. Accordingly, sustained Wnt/β-catenin signaling maintains normal ICR methylation and mESC homeostasis and is a key regulator of genome stability.
dc.description.sponsorshipWe acknowledge the support from Spanish Ministry of Economy and Competitiveness and FEDER funds (SAF2011-28580, BFU2014-54717-P, BFU2017-86760-P and BFU2015-71984-ERC to M.P.C.), as well as ‘Centro de Excelencia Severo Ochoa 2013–2017’, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya grant (2014 SGR1137 to M.P.C.), AGAUR (SGR 2017-2019 to M.P.C) and the CERCA Programme/Generalitat de Catalunya (to M.P.C.), the European Union’s Horizon 2020 research and innovation programme under grant agreement CellViewer No 686637 (to M.P.C.), People Programme Marie Curie Actions of the European Union’s Seventh Framework Programme (FP7/2007–2013/, n° 290123 to I.T.), La Caixa international PhD fellowship (to F.S.) and Ministerio de Ciencia e Innovació FPI (to F.A.) and People Program (Marie Curie Actions) FP7/2007–2013 under REA grant (608959 to M.V.N.).
dc.format.mimetypeapplication/pdf
dc.identifier.citationTheka I, Sottile F, Cammisa M, Bonnin S, Sanchez-Delgado M, Di Vicino U, Neguembor MV, Arumugam K, Aulicino F, Monk D, Riccio A, Cosma MP. Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells. Sci Rep. 2019; 9(1):948. DOI 10.1038/s41598-018-37442-5
dc.identifier.doihttp://dx.doi.org/10.1038/s41598-018-37442-5
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10230/36888
dc.language.isoeng
dc.publisherNature Research
dc.relation.ispartofSci Rep. 2019; 9(1):948
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/SAF2011-28580
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/BFU2014-54717-P
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/1PE/BFU2015-71984-ERC
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/686637
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/290123
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/608959
dc.rights© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.keywordEmbryonic stem cells
dc.subject.keywordStem-cell differentiation
dc.titleWnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells
dc.typeinfo:eu-repo/semantics/article
dc.type.versioninfo:eu-repo/semantics/publishedVersion

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