Embryonic Stem Cells/Induced Pluripotent Stem Cells

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E-Cadherin-Mediated Cell–Cell Contact Is Critical for Induced Pluripotent Stem Cell Generation†‡§

  1. Taotao Chen1,
  2. Detian Yuan1,
  3. Bin Wei1,
  4. Jing Jiang1,
  5. Jiuhong Kang1,2,
  6. Kun Ling3,
  7. Yijun Gu1,
  8. Jinsong Li1,
  9. Lei Xiao1,
  10. Gang Pei1,2,¶,*

Article first published online: 2 JUN 2010

DOI: 10.1002/stem.456

Issue

STEM CELLS

STEM CELLS

Volume 28, Issue 8, pages 1315–1325, August 2010

Additional Information

How to Cite

Chen, T., Yuan, D., Wei, B., Jiang, J., Kang, J., Ling, K., Gu, Y., Li, J., Xiao, L. and Pei, G. (2010), E-Cadherin-Mediated Cell–Cell Contact Is Critical for Induced Pluripotent Stem Cell Generation. STEM CELLS, 28: 1315–1325. doi: 10.1002/stem.456

Author Information

  1. 1

    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

  2. 2

    Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, China

  3. 3

    Department of Biochemistry and Molecular Biology, Mayo Clinic Cancer Center, Rochester, Minnesota, USA

  1. Tel: +86-21-54921373; fax: +86-21-54921372

*Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

  1. †

    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.

  2. ‡

    Disclosure of potential conflicts of interest is found at the end of this article.

  3. §

    First published online in STEM CELLS EXPRESS June 2, 2010.

Publication History

  1. Issue published online: 18 AUG 2010
  2. Article first published online: 2 JUN 2010
  3. Manuscript Accepted: 21 MAY 2010
  4. Manuscript Received: 23 MAR 2010

Funded by

  • Ministry of Science and Technology. Grant Numbers: 2007CB947904, 2007CB947100, 2007CB948000, 2009CB9 41100, 2009CB940903, 2010CB944900
  • National Natural Science Foundation of China. Grant Numbers: 30625014, 30623003, 30871285, 90713047, 90919028, 30871430
  • Shanghai Municipal Commission for Science and Technology. Grant Numbers: 07DZ22919, 08dj1400500, 08dj1400502, 09PJ1410900
  • Natural Science Foundation of Shanghai. Grant Number: 10ZR1435300
  • Chinese Academy of Sciences. Grant Numbers: SIBS2008001, KSCX2-YW-R-110, KSCX2-YW-R-229

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Keywords:

  • Cell adhesion molecules;
  • Reprograming;
  • Induced pluripotent stem;
  • Embryonic stem cells

Abstract

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

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