E‐Cadherin‐Mediated Cell–Cell Contact Is Critical for Induced Pluripotent Stem Cell Generation

The low efficiency of reprogramming and genomic integration of virus vectors obscure the potential application of induced pluripotent stem (iPS) cells; therefore, identification of chemicals and cooperative factors that may improve the generation of iPS cells will be of great value. Moreover, the ce...

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Published inStem cells (Dayton, Ohio) Vol. 28; no. 8; pp. 1315 - 1325
Main Authors Chen, Taotao, Yuan, Detian, Wei, Bin, Jiang, Jing, Kang, Jiuhong, Ling, Kun, Gu, Yijun, Li, Jinsong, Xiao, Lei, Pei, Gang
Format Journal Article
LanguageEnglish
Published Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2010
Subjects
Animals
Apigenin - pharmacology
Blotting, Western
Cadherins - genetics
Cadherins - metabolism
Cell adhesion molecules
Cells, Cultured
Cellular Reprogramming - drug effects
Cellular Reprogramming - genetics
Cellular Reprogramming - physiology
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - drug effects
Embryonic Stem Cells - metabolism
Flow Cytometry
Gene Expression - drug effects
Induced pluripotent stem
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - drug effects
Induced Pluripotent Stem Cells - metabolism
Luteolin - pharmacology
Mice
Reprograming
Reverse Transcriptase Polymerase Chain Reaction
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Summary:The low efficiency of reprogramming and genomic integration of virus vectors obscure the potential application of induced pluripotent stem (iPS) cells; therefore, identification of chemicals and cooperative factors that may improve the generation of iPS cells will be of great value. Moreover, the cellular mechanisms that limit the reprogramming efficiency need to be investigated. Through screening a chemical library, we found that two chemicals reported to upregulate E‐cadherin considerably increase the reprogramming efficiency. Further study of the process indicated that E‐cadherin is upregulated during reprogramming and the established iPS cells possess E‐cadherin‐mediated cell–cell contact, morphologically indistinguishable from embryonic stem (ES) cells. Our experiments also demonstrate that overexpression of E‐cadherin significantly enhances reprogramming efficiency, whereas knockdown of endogenous E‐cadherin reduces the efficiency. Consistently, abrogation of cell–cell contact by the inhibitory peptide or the neutralizing antibody against the extracellular domain of E‐cadherin compromises iPS cell generation. Further mechanistic study reveals that adhesive binding activity of E‐cadherin is required. Our results highlight the critical role of E‐cadherin‐mediated cell–cell contact in reprogramming and suggest new routes for more efficient iPS cell generation. STEM CELLS 2010;28:1315–1325
Bibliography:First published online in STEM CELLS
June 2, 2010.
Tel: +86‐21‐54921373; fax: +86‐21‐54921372
Disclosure of potential conflicts of interest is found at the end of this article.
Author contributions: T.C.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; D.Y.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; B.W.: data analysis and interpretation, manuscript writing; J.J.: collection and/or assembly of data, data analysis and interpretation; J.K.: data analysis and interpretation; K.L.: data analysis and interpretation; Y.G.: collection and/or assembly of data; J.L.: data analysis and interpretation; L.X.: data analysis and interpretation; G.P.: conception and design, data analysis and interpretation, manuscript writing, financial and administrative support, and final approval of manuscript. T.C. and D.Y. contributed equally to this work.
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ISSN:1066-5099
1549-4918
DOI:10.1002/stem.456