Connexin 43 is involved in the generation of human-induced pluripotent stem cells

Qiong Ke, Li Li, Bing Cai, Chang Liu, Yan Yang, Yong Gao, Weijun Huang, Xiaofeng Yuan, Tao Wang, Qi Zhang, Andrew L. Harris, Liang Tao, Andy Peng Xiang

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Although somatic cells can be successfully programmed to create pluripotent stem cells by ectopically expressing defined transcriptional factors, reprogramming efficiency is low and the reprogramming mechanism remains unclear. Previous reports have shown that almost all human connexin (CX) isoforms are expressed by human embryonic stem (hES) cells and that gap junctional intercellular communication (GJIC) is important for ES cell survival and differentiation. However, the CX expression profiles in human induced pluripotent stem (iPS) cells and the role of CXs in the process of reprogramming back to iPS cells remains unknown. Here, we determined the expression levels of most forms of CX in human embryonic fibroblasts (hEFs) and in the hEFderived iPS cells. A scrape loading/dye transfer assay showed that human iPS cells contained functional gap junctions (GJs) that could be affected by pharmacological inhibitors of GJ function. We found that CX43 was the most dramatically upregulated CX following reprogramming. Most importantly, the ectopic expression of CX43 significantly enhanced the reprogramming efficiency, whereas shRNA-mediated knockdown of endogenous CX43 expression greatly reduced the efficiency. In addition, we found that CX43 overexpression or knockdown affected the expression of E-CADHERIN, a marker of the mesenchymal-to-epithelial transition (MET), during reprogramming. In conclusion, our data indicate that CX43 expression is important for reprogramming and may mediate the MET that is associated with the acquisition of pluripotency.

Original languageEnglish (US)
Pages (from-to)2221-2233
Number of pages13
JournalHuman molecular genetics
Volume22
Issue number11
DOIs
StatePublished - Jun 2013

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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