E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation

Taotao Chen, Detian Yuan, Bin Wei, Jing Jiang, Jiuhong Kang, Kun Ling, Yijun Gu, Jinsong Li, Lei Xiao, Gang Pei

Research output: Contribution to journalArticle

161 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalStem Cells
Volume28
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Induced Pluripotent Stem Cells
Cadherins
Small Molecule Libraries
Virus Integration
Embryonic Stem Cells
Neutralizing Antibodies
Adhesives
Up-Regulation
Peptides

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. / Chen, Taotao; Yuan, Detian; Wei, Bin; Jiang, Jing; Kang, Jiuhong; Ling, Kun; Gu, Yijun; Li, Jinsong; Xiao, Lei; Pei, Gang.

In: Stem Cells, Vol. 28, No. 8, 08.2010, p. 1315-1325.

Research output: Contribution to journalArticle

Chen, T, Yuan, D, Wei, B, Jiang, J, Kang, J, Ling, K, Gu, Y, Li, J, Xiao, L & Pei, G 2010, 'E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation', Stem Cells, vol. 28, no. 8, pp. 1315-1325. https://doi.org/10.1002/stem.456
Chen, Taotao ; Yuan, Detian ; Wei, Bin ; Jiang, Jing ; Kang, Jiuhong ; Ling, Kun ; Gu, Yijun ; Li, Jinsong ; Xiao, Lei ; Pei, Gang. / E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation. In: Stem Cells. 2010 ; Vol. 28, No. 8. pp. 1315-1325.
@article{738181986125494a8af12aa119ca28a3,
title = "E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation",
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.",
keywords = "Cell adhesion molecules, Embryonic stem cells, Induced pluripotent stem, Reprograming",
author = "Taotao Chen and Detian Yuan and Bin Wei and Jing Jiang and Jiuhong Kang and Kun Ling and Yijun Gu and Jinsong Li and Lei Xiao and Gang Pei",
year = "2010",
month = "8",
doi = "10.1002/stem.456",
language = "English (US)",
volume = "28",
pages = "1315--1325",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - E-cadherin-mediated cell-cell contact is critical for induced pluripotent stem cell generation

AU - Chen, Taotao

AU - Yuan, Detian

AU - Wei, Bin

AU - Jiang, Jing

AU - Kang, Jiuhong

AU - Ling, Kun

AU - Gu, Yijun

AU - Li, Jinsong

AU - Xiao, Lei

AU - Pei, Gang

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Cell adhesion molecules

KW - Embryonic stem cells

KW - Induced pluripotent stem

KW - Reprograming

UR - http://www.scopus.com/inward/record.url?scp=77955801632&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955801632&partnerID=8YFLogxK

U2 - 10.1002/stem.456

DO - 10.1002/stem.456

M3 - Article

C2 - 20521328

AN - SCOPUS:77955801632

VL - 28

SP - 1315

EP - 1325

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

IS - 8

ER -