title: Connexin 43 is involved in the generation of human-induced pluripotent stem cells.
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 hEF-derived 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.
authors: Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education.
authors: Qiong
authors: Q
authors: Ke
authors: Li
authors: L
authors: Li
authors: Bing
authors: B
authors: Cai
authors: Chang
authors: C
authors: Liu
authors: Yan
authors: Y
authors: Yang
authors: Yong
authors: Y
authors: Gao
authors: Weijun
authors: W
authors: Huang
authors: Xiaofeng
authors: X
authors: Yuan
authors: Tao
authors: T
authors: Wang
authors: Qi
authors: Q
authors: Zhang
authors: Andrew L
authors: AL
authors: Harris
authors: Liang
authors: L
authors: Tao
authors: Andy Peng
authors: AP
authors: Xiang
mesh_terms: D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D017629:Gap Junctions / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism*
chemical_list: D015820:Cadherins; D018031:Connexin 43