Wnt/ß-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells.
Sci Rep
; 9(1): 948, 2019 01 30.
Article
em En
| MEDLINE
| ID: mdl-30700782
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/ß-catenin signaling pathway, which is essential for mESC differentiation and proliferation. Here we show that the activity of the Wnt/ß-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/ß-catenin signaling maintains normal ICR methylation and mESC homeostasis and is a key regulator of genome stability.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Epigênese Genética
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Proliferação de Células
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Via de Sinalização Wnt
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Células-Tronco Embrionárias Murinas
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Homeostase
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article