Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions

Dong Li, Jiaxi Zhou, Lu Wang, Myung Eun Shin, Pei Su, Xiaohua Lei, Haibin Kuang, Weixiang Guo, Hong Yang, Linzhao Cheng, Tetsuya S. Tanaka, Deborah E. Leckband, Albert B. Reynolds, Enkui Duan, Fei Wang

Research output: Contribution to journalArticle

Abstract

Human embryonic stem cells (ESCs [hESCs]) proliferate as colonies wherein individual cells are strongly adhered to one another. This architecture is linked to hESC self-renewal, pluripotency, and survival and depends on epithelial cadherin (E-cadherin), NMMIIA (nonmuscle myosin IIA), and p120-catenin. E-cadherin and p120-catenin work within a positive feedback loop that promotes localized accumulation of E-cadherin at intercellular junctions. NMMIIA stabilizes p120-catenin protein and controls E-cadherin-mediated intercellular adhesion. Perturbations of this signaling network disrupt colony formation, destabilize the transcriptional regulatory circuitry for pluripotency, and impair long-term survival of hESCs. Furthermore, depletion of E-cadherin markedly reduces the efficiency of reprogramming of human somatic cells to an ESC-like state. The feedback regulation and mechanical-biochemical integration provide mechanistic insights for the regulation of intercellular adhesion and cellular architecture in hESCs during longterm self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.

Original languageEnglish (US)
Pages (from-to)631-644
Number of pages14
JournalJournal of Cell Biology
Volume191
Issue number3
DOIs
StatePublished - Nov 1 2010

Fingerprint

Cadherins
Nonmuscle Myosin Type IIA
Physiological Feedback
Intercellular Junctions
Survival
Human Embryonic Stem Cells
delta catenin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions. / Li, Dong; Zhou, Jiaxi; Wang, Lu; Shin, Myung Eun; Su, Pei; Lei, Xiaohua; Kuang, Haibin; Guo, Weixiang; Yang, Hong; Cheng, Linzhao; Tanaka, Tetsuya S.; Leckband, Deborah E.; Reynolds, Albert B.; Duan, Enkui; Wang, Fei.

In: Journal of Cell Biology, Vol. 191, No. 3, 01.11.2010, p. 631-644.

Research output: Contribution to journalArticle

Li, D, Zhou, J, Wang, L, Shin, ME, Su, P, Lei, X, Kuang, H, Guo, W, Yang, H, Cheng, L, Tanaka, TS, Leckband, DE, Reynolds, AB, Duan, E & Wang, F 2010, 'Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions', Journal of Cell Biology, vol. 191, no. 3, pp. 631-644. https://doi.org/10.1083/jcb.201006094
Li, Dong ; Zhou, Jiaxi ; Wang, Lu ; Shin, Myung Eun ; Su, Pei ; Lei, Xiaohua ; Kuang, Haibin ; Guo, Weixiang ; Yang, Hong ; Cheng, Linzhao ; Tanaka, Tetsuya S. ; Leckband, Deborah E. ; Reynolds, Albert B. ; Duan, Enkui ; Wang, Fei. / Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions. In: Journal of Cell Biology. 2010 ; Vol. 191, No. 3. pp. 631-644.
@article{9c423bf7bfca4b0fa4f625a167785833,
title = "Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions",
abstract = "Human embryonic stem cells (ESCs [hESCs]) proliferate as colonies wherein individual cells are strongly adhered to one another. This architecture is linked to hESC self-renewal, pluripotency, and survival and depends on epithelial cadherin (E-cadherin), NMMIIA (nonmuscle myosin IIA), and p120-catenin. E-cadherin and p120-catenin work within a positive feedback loop that promotes localized accumulation of E-cadherin at intercellular junctions. NMMIIA stabilizes p120-catenin protein and controls E-cadherin-mediated intercellular adhesion. Perturbations of this signaling network disrupt colony formation, destabilize the transcriptional regulatory circuitry for pluripotency, and impair long-term survival of hESCs. Furthermore, depletion of E-cadherin markedly reduces the efficiency of reprogramming of human somatic cells to an ESC-like state. The feedback regulation and mechanical-biochemical integration provide mechanistic insights for the regulation of intercellular adhesion and cellular architecture in hESCs during longterm self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.",
author = "Dong Li and Jiaxi Zhou and Lu Wang and Shin, {Myung Eun} and Pei Su and Xiaohua Lei and Haibin Kuang and Weixiang Guo and Hong Yang and Linzhao Cheng and Tanaka, {Tetsuya S.} and Leckband, {Deborah E.} and Reynolds, {Albert B.} and Enkui Duan and Fei Wang",
year = "2010",
month = "11",
day = "1",
doi = "10.1083/jcb.201006094",
language = "English (US)",
volume = "191",
pages = "631--644",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions

AU - Li, Dong

AU - Zhou, Jiaxi

AU - Wang, Lu

AU - Shin, Myung Eun

AU - Su, Pei

AU - Lei, Xiaohua

AU - Kuang, Haibin

AU - Guo, Weixiang

AU - Yang, Hong

AU - Cheng, Linzhao

AU - Tanaka, Tetsuya S.

AU - Leckband, Deborah E.

AU - Reynolds, Albert B.

AU - Duan, Enkui

AU - Wang, Fei

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Human embryonic stem cells (ESCs [hESCs]) proliferate as colonies wherein individual cells are strongly adhered to one another. This architecture is linked to hESC self-renewal, pluripotency, and survival and depends on epithelial cadherin (E-cadherin), NMMIIA (nonmuscle myosin IIA), and p120-catenin. E-cadherin and p120-catenin work within a positive feedback loop that promotes localized accumulation of E-cadherin at intercellular junctions. NMMIIA stabilizes p120-catenin protein and controls E-cadherin-mediated intercellular adhesion. Perturbations of this signaling network disrupt colony formation, destabilize the transcriptional regulatory circuitry for pluripotency, and impair long-term survival of hESCs. Furthermore, depletion of E-cadherin markedly reduces the efficiency of reprogramming of human somatic cells to an ESC-like state. The feedback regulation and mechanical-biochemical integration provide mechanistic insights for the regulation of intercellular adhesion and cellular architecture in hESCs during longterm self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.

AB - Human embryonic stem cells (ESCs [hESCs]) proliferate as colonies wherein individual cells are strongly adhered to one another. This architecture is linked to hESC self-renewal, pluripotency, and survival and depends on epithelial cadherin (E-cadherin), NMMIIA (nonmuscle myosin IIA), and p120-catenin. E-cadherin and p120-catenin work within a positive feedback loop that promotes localized accumulation of E-cadherin at intercellular junctions. NMMIIA stabilizes p120-catenin protein and controls E-cadherin-mediated intercellular adhesion. Perturbations of this signaling network disrupt colony formation, destabilize the transcriptional regulatory circuitry for pluripotency, and impair long-term survival of hESCs. Furthermore, depletion of E-cadherin markedly reduces the efficiency of reprogramming of human somatic cells to an ESC-like state. The feedback regulation and mechanical-biochemical integration provide mechanistic insights for the regulation of intercellular adhesion and cellular architecture in hESCs during longterm self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.

UR - http://www.scopus.com/inward/record.url?scp=78049520763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78049520763&partnerID=8YFLogxK

U2 - 10.1083/jcb.201006094

DO - 10.1083/jcb.201006094

M3 - Article

C2 - 20974810

AN - SCOPUS:78049520763

VL - 191

SP - 631

EP - 644

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 3

ER -