Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45

Abstract Somatic cells can be successfully reprogrammed into pluripotent stem cells by the ectopic expression of defined transcriptional factors. However, improved efficiency and better understanding the molecular mechanism underlying reprogramming are still required. In the present study, a scrape...

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Autores principales: Qiong Ke, Li Li, Xin Yao, Xingqiang Lai, Bing Cai, Hong Chen, Rui Chen, Zhichen Zhai, Lihua Huang, Kai Li, Anbin Hu, Frank Fuxiang Mao, Andy Peng Xiang, Liang Tao, Weiqiang Li
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/906eb03518ef4a0b839b9077d086759e
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spelling oai:doaj.org-article:906eb03518ef4a0b839b9077d086759e2021-12-02T12:30:53ZEnhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 4510.1038/s41598-017-00523-y2045-2322https://doaj.org/article/906eb03518ef4a0b839b9077d086759e2017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00523-yhttps://doaj.org/toc/2045-2322Abstract Somatic cells can be successfully reprogrammed into pluripotent stem cells by the ectopic expression of defined transcriptional factors. However, improved efficiency and better understanding the molecular mechanism underlying reprogramming are still required. In the present study, a scrape loading/dye transfer assay showed that human induced pluripotent stem cells (hiPSCs) contained functional gap junctions partially contributed by Connexin 45 (CX45). We then found CX45 was expressed in human embryonic stem cells (hESCs) and human dermal fibroblasts (hDFs) derived hiPSCs. Then we showed that CX45 was dramatically upregulated during the reprogramming process. Most importantly, the ectopic expression of CX45 significantly enhanced the reprogramming efficiency together with the Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM), whereas knockdown of endogenous CX45 expression significantly blocked cellular reprogramming and reduced the efficiency. Our further study demonstrated that CX45 overexpression or knockdown modulated the cell proliferation rate which was associated with the reprogramming efficiency. In conclusion, our data highlighted the critical role of CX45 in reprogramming and may increase the cell division rate and result in an accelerated kinetics of iPSCs production.Qiong KeLi LiXin YaoXingqiang LaiBing CaiHong ChenRui ChenZhichen ZhaiLihua HuangKai LiAnbin HuFrank Fuxiang MaoAndy Peng XiangLiang TaoWeiqiang LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Qiong Ke
Li Li
Xin Yao
Xingqiang Lai
Bing Cai
Hong Chen
Rui Chen
Zhichen Zhai
Lihua Huang
Kai Li
Anbin Hu
Frank Fuxiang Mao
Andy Peng Xiang
Liang Tao
Weiqiang Li
Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
description Abstract Somatic cells can be successfully reprogrammed into pluripotent stem cells by the ectopic expression of defined transcriptional factors. However, improved efficiency and better understanding the molecular mechanism underlying reprogramming are still required. In the present study, a scrape loading/dye transfer assay showed that human induced pluripotent stem cells (hiPSCs) contained functional gap junctions partially contributed by Connexin 45 (CX45). We then found CX45 was expressed in human embryonic stem cells (hESCs) and human dermal fibroblasts (hDFs) derived hiPSCs. Then we showed that CX45 was dramatically upregulated during the reprogramming process. Most importantly, the ectopic expression of CX45 significantly enhanced the reprogramming efficiency together with the Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM), whereas knockdown of endogenous CX45 expression significantly blocked cellular reprogramming and reduced the efficiency. Our further study demonstrated that CX45 overexpression or knockdown modulated the cell proliferation rate which was associated with the reprogramming efficiency. In conclusion, our data highlighted the critical role of CX45 in reprogramming and may increase the cell division rate and result in an accelerated kinetics of iPSCs production.
format article
author Qiong Ke
Li Li
Xin Yao
Xingqiang Lai
Bing Cai
Hong Chen
Rui Chen
Zhichen Zhai
Lihua Huang
Kai Li
Anbin Hu
Frank Fuxiang Mao
Andy Peng Xiang
Liang Tao
Weiqiang Li
author_facet Qiong Ke
Li Li
Xin Yao
Xingqiang Lai
Bing Cai
Hong Chen
Rui Chen
Zhichen Zhai
Lihua Huang
Kai Li
Anbin Hu
Frank Fuxiang Mao
Andy Peng Xiang
Liang Tao
Weiqiang Li
author_sort Qiong Ke
title Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
title_short Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
title_full Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
title_fullStr Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
title_full_unstemmed Enhanced generation of human induced pluripotent stem cells by ectopic expression of Connexin 45
title_sort enhanced generation of human induced pluripotent stem cells by ectopic expression of connexin 45
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/906eb03518ef4a0b839b9077d086759e
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