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- Title
Integrated biochemical and mechanical signals regulate multifaceted human embryonic stem cell functions.
- Authors
Dong Li; Jiaxi Zhou; Lu Wang; Myung Eun Shin; Pei Su; Xiaohua Lei; Haibin Kuang; Weixiang Guo; Hong Yang; Linzhao Cheng; Tanaka, Tetsuya S.; Leckband, Deborah E.; Reynolds, Albert B.; Enkui Duan; Fei Wang
- 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 long-term self-renewal. Our findings also contribute to the understanding of microenvironmental regulation of hESC identity and somatic reprogramming.
- Subjects
EMBRYONIC stem cells; CELLULAR mechanics; STEM cells; CADHERINS; MYOSIN
- Publication
Journal of Cell Biology, 2010, Vol 191, Issue 3, p631
- ISSN
0021-9525
- Publication type
Article
- DOI
10.1083/jcb.201006094