2018
DOI: 10.1002/stem.2788
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Wnt/β-Catenin/TCF Pathway Is a Phase-Dependent Promoter of Colony Formation and Mesendodermal Differentiation During Human Somatic Cell Reprogramming

Abstract: Somatic cell reprogramming is a biphasic phenomenon that goes through a mesenchymal-to-epithelial transition, called initiation phase, followed by a maturation phase wherein reprogramming cells acquire pluripotency. Here, we show that these phases display a differential response to Wnt signaling activation. Wnt signaling increases colony formation by promoting cellular epithelialization during the initiation phase in a TCF7-dependent manner. However, during maturation phase, it is also responsible for inducing… Show more

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Cited by 15 publications
(20 citation statements)
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“…Inhibiting chromatin H3K79 methyltransferase DOT1L improves OSKM-induced reprogramming efficiency from human fibroblasts 13 . Also, inhibiting canonical WNT/β-CATENIN signaling at late reprogramming stage prevents differentiation of the reprogrammed cells 20 . We have shown that the DOT1L inhibitor (iDOT1L) 13 and canonical WNT signaling inhibitor (IWR1) 21 improve total TRA-1-60+ colony number and the homogeneity of individual TRA-1-60+ colonies, respectively 19 .…”
Section: Resultsmentioning
confidence: 99%
“…Inhibiting chromatin H3K79 methyltransferase DOT1L improves OSKM-induced reprogramming efficiency from human fibroblasts 13 . Also, inhibiting canonical WNT/β-CATENIN signaling at late reprogramming stage prevents differentiation of the reprogrammed cells 20 . We have shown that the DOT1L inhibitor (iDOT1L) 13 and canonical WNT signaling inhibitor (IWR1) 21 improve total TRA-1-60+ colony number and the homogeneity of individual TRA-1-60+ colonies, respectively 19 .…”
Section: Resultsmentioning
confidence: 99%
“…Overexpression of TCF7L1 causes downregulation of mesodermal gene expression, and leads to an improved somatic cell reprogramming and colony formation [81]. However, stabilization of βcatenin has been shown to also enhance self-renewal in naïve mouse ESCs in a TCF independent manner, whereby nuclear β-catenin acts by directly interacting with the master transcription factor, OCT4, to induce the expression of pluripotent genes [82].…”
Section: Discussionmentioning
confidence: 99%
“…Some researchers have studied the effect of miR-21 on the Wnt signaling pathway by stably transfecting miR-21-overexpressing HCT-116 cells. Their results indicated that miR-21 overexpression leads to the activation of Wnt/β-catenin signaling, such as decreased levels of axin (a negative regulator of the Wnt signaling pathway), increased levels of β-catenin, the induction of TCF/LEF (a group of transcription factors that bind to DNA through a high-mobility group domain and are involved in the Wnt signaling pathway) activity, and the increased expression of the downstream target proteins c-Myc and cyclin D1 (3236). These conclusions are consistent with our present results.…”
Section: Discussionmentioning
confidence: 99%