Publication:20190207100331
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| Publication | |
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| URL | https://www.ncbi.nlm.nih.gov/pubmed/30700782 |
| Title | Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells
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| Authors | Ilda Theka, Francesco Sottile, Marco Cammisa, Sarah Bonnin, Marta Sanchez-Delgado, Umberto Di Vicino, Maria Victoria Neguembor, Karthik Arumugam, Francesco Aulicino, David Monk, Andrea Riccio, Maria Pia Cosma |
| Date | 2019-01-30
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| Publisher | Scientific Reports |
| DOI | 10.1038/s41598-018-37442-5 |
| Tag | Animals, Cell Differentiation, Cell Line, Cell Proliferation, DNA Methylation, Epigenesis, Genetic, Homeostasis, Mice, Mouse Embryonic Stem Cells, Wnt Signaling Pathway |
Abstract:
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.
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.
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