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

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Li, D., Zhou, J., Wang, L., Shin, M. E., Su, P., Lei, X., Kuang, H., Guo, W., Yang, H., Cheng, L., Tanaka, T. S., Leckband, D. E., Reynolds, A. B., Duan, E., & Wang, F. (2010). Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions. Journal of Cell Biology, 191(3), 631-644. https://doi.org/10.1083/jcb.201006094