Title: Temporal perturbation of the Wnt signaling pathway in the control of cell reprogramming is modulated by TCF1
Authors: Aulicino, Francesco
Theka, Ilda
Ombrato, Luigi
Lluis, Frederic # ×
Cosma, Maria Pia #
Issue Date: May-2014
Publisher: Cell Press
Series Title: Stem Cell Reports vol:2 issue:5 pages:707-20
Article number: 10.1016/j.stemcr.2014.04.001
Abstract: Cyclic activation of the Wnt/β-catenin signaling pathway controls cell fusion-mediated somatic cell reprogramming. TCFs belong to a family of transcription factors that, in complex with β-catenin, bind and transcriptionally regulate Wnt target genes. Here, we show that Wnt/β-catenin signaling needs to be off during the early reprogramming phases of mouse embryonic fibroblasts (MEFs) into iPSCs. In MEFs undergoing reprogramming, senescence genes are repressed and mesenchymal-to-epithelial transition is favored. This is correlated with a repressive activity of TCF1, which contributes to the silencing of Wnt/β-catenin signaling at the onset of reprogramming. In contrast, the Wnt pathway needs to be active in the late reprogramming phases to achieve successful reprogramming. In conclusion, continued activation or inhibition of the Wnt/β-catenin signaling pathway is detrimental to the reprogramming of MEFs; instead, temporal perturbation of the pathway is essential for efficient reprogramming, and the "Wnt-off" state can be considered an early reprogramming marker.
ISSN: 2213-6711
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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