Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1
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...
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doaj-0d2d95e62ca24034b60319aa17fcb1b82020-11-25T01:06:24ZengElsevierStem Cell Reports2213-67112014-05-012570772010.1016/j.stemcr.2014.04.001Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1Francesco Aulicino0Ilda Theka1Luigi Ombrato2Frederic Lluis3Maria Pia Cosma4Centre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), Dr. Aiguader 88, 08003 Barcelona, SpainCyclic 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.http://www.sciencedirect.com/science/article/pii/S2213671114001088 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Francesco Aulicino Ilda Theka Luigi Ombrato Frederic Lluis Maria Pia Cosma |
spellingShingle |
Francesco Aulicino Ilda Theka Luigi Ombrato Frederic Lluis Maria Pia Cosma Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 Stem Cell Reports |
author_facet |
Francesco Aulicino Ilda Theka Luigi Ombrato Frederic Lluis Maria Pia Cosma |
author_sort |
Francesco Aulicino |
title |
Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 |
title_short |
Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 |
title_full |
Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 |
title_fullStr |
Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 |
title_full_unstemmed |
Temporal Perturbation of the Wnt Signaling Pathway in the Control of Cell Reprogramming Is Modulated by TCF1 |
title_sort |
temporal perturbation of the wnt signaling pathway in the control of cell reprogramming is modulated by tcf1 |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2014-05-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671114001088 |
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