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

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
J Cell Biol. 2010 191 (3): 631-44

PMID: 20974810 · PMCID: PMC3003326 · DOI:10.1083/jcb.201006094

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 long-term self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.

MeSH Terms (7)

Cadherins Catenins Cells, Cultured Embryonic Stem Cells Humans Nonmuscle Myosin Type IIA Signal Transduction

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