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

Mouse 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/...

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Detalles Bibliográficos
Autores: Theka, Ilda, 1984-, Sottile, Francesco, 1988-, Cammisa, Marco, Bonnin, Sarah, Sanchez-Delgado, Marta, Di Vicino, Umberto, Neguembor, Maria Victoria, Arumugam, Karthik, Aulicino, Francesco, 1987-, Monk, David, Riccio, Andrea, Cosma, Maria Pia, 1970-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/36888
Acceso en línea:http://hdl.handle.net/10230/36888
http://dx.doi.org/10.1038/s41598-018-37442-5
Access Level:acceso abierto
Palabra clave:Embryonic stem cells
Stem-cell differentiation
Descripción
Sumario:Mouse 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.