Theka, Ilda, 1984-Sottile, Francesco, 1988-Cammisa, MarcoBonnin, SarahSanchez-Delgado, MartaDi Vicino, UmbertoNeguembor, Maria VictoriaArumugam, KarthikAulicino, Francesco, 1987-Monk, DavidRiccio, AndreaCosma, Maria Pia, 1970-2019-03-222019-03-222019Theka 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/s41598-018-37442-52045-2322http://hdl.handle.net/10230/36888Mouse 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.application/pdfeng© 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/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-018-37442-5Embryonic stem cellsStem-cell differentiationinfo:eu-repo/semantics/openAccess