TY - JOUR
T1 - Wnt/β-catenin signaling pathway safeguards epigenetic stability and homeostasis of mouse embryonic stem cells
AU - Theka, Ilda
AU - Sottile, Francesco
AU - Cammisa, Marco
AU - Bonnin, Sarah
AU - Sanchez-Delgado, Marta
AU - Di Vicino, Umberto
AU - Neguembor, Maria Victoria
AU - Arumugam, Karthik
AU - Aulicino, Francesco
AU - Monk, David
AU - Riccio, Andrea
AU - Cosma, Maria Pia
PY - 2019/1/30
Y1 - 2019/1/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85060950560&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-37442-5
DO - 10.1038/s41598-018-37442-5
M3 - Article (Academic Journal)
C2 - 30700782
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
M1 - 948
ER -