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TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition

Transcription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles of Tfap2c in regulating somatic cell reprogramming...

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Autores principales: Wang, Yuan, Chen, Shuang, Jiang, Qingyuan, Deng, Jie, Cheng, Fuyi, Lin, Yi, Cheng, Lin, Ye, Yixin, Chen, Xiaolei, Yao, Yunqi, Zhang, Xiaomei, Shi, Gang, Dai, Lei, Su, Xiaolan, Peng, Yong, Deng, Hongxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316975/
https://www.ncbi.nlm.nih.gov/pubmed/32587258
http://dx.doi.org/10.1038/s41419-020-2684-9
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author Wang, Yuan
Chen, Shuang
Jiang, Qingyuan
Deng, Jie
Cheng, Fuyi
Lin, Yi
Cheng, Lin
Ye, Yixin
Chen, Xiaolei
Yao, Yunqi
Zhang, Xiaomei
Shi, Gang
Dai, Lei
Su, Xiaolan
Peng, Yong
Deng, Hongxin
author_facet Wang, Yuan
Chen, Shuang
Jiang, Qingyuan
Deng, Jie
Cheng, Fuyi
Lin, Yi
Cheng, Lin
Ye, Yixin
Chen, Xiaolei
Yao, Yunqi
Zhang, Xiaomei
Shi, Gang
Dai, Lei
Su, Xiaolan
Peng, Yong
Deng, Hongxin
author_sort Wang, Yuan
collection PubMed
description Transcription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles of Tfap2c in regulating somatic cell reprogramming are not well understood. Here we demonstrate Tfap2c is induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression. Meanwhile, Tfap2c can greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets of Tfap2c during reprogramming by RNA-sequencing (RNA-seq) and ChIP-qPCR indicates that TFAP2C can promote epithelial gene expression by binding to their promoters directly. Finally, knockdown of E-cadherin (Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizes Tfap2c-mediated reprogramming. Taken together, we conclude that Tfap2c serves as a strong activator for somatic cell reprogramming through promoting the MET and inhibiting c-Myc-dependent apoptosis.
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spelling pubmed-73169752020-06-30 TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition Wang, Yuan Chen, Shuang Jiang, Qingyuan Deng, Jie Cheng, Fuyi Lin, Yi Cheng, Lin Ye, Yixin Chen, Xiaolei Yao, Yunqi Zhang, Xiaomei Shi, Gang Dai, Lei Su, Xiaolan Peng, Yong Deng, Hongxin Cell Death Dis Article Transcription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles of Tfap2c in regulating somatic cell reprogramming are not well understood. Here we demonstrate Tfap2c is induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression. Meanwhile, Tfap2c can greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets of Tfap2c during reprogramming by RNA-sequencing (RNA-seq) and ChIP-qPCR indicates that TFAP2C can promote epithelial gene expression by binding to their promoters directly. Finally, knockdown of E-cadherin (Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizes Tfap2c-mediated reprogramming. Taken together, we conclude that Tfap2c serves as a strong activator for somatic cell reprogramming through promoting the MET and inhibiting c-Myc-dependent apoptosis. Nature Publishing Group UK 2020-06-25 /pmc/articles/PMC7316975/ /pubmed/32587258 http://dx.doi.org/10.1038/s41419-020-2684-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Wang, Yuan
Chen, Shuang
Jiang, Qingyuan
Deng, Jie
Cheng, Fuyi
Lin, Yi
Cheng, Lin
Ye, Yixin
Chen, Xiaolei
Yao, Yunqi
Zhang, Xiaomei
Shi, Gang
Dai, Lei
Su, Xiaolan
Peng, Yong
Deng, Hongxin
TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title_full TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title_fullStr TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title_full_unstemmed TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title_short TFAP2C facilitates somatic cell reprogramming by inhibiting c-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
title_sort tfap2c facilitates somatic cell reprogramming by inhibiting c-myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316975/
https://www.ncbi.nlm.nih.gov/pubmed/32587258
http://dx.doi.org/10.1038/s41419-020-2684-9
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