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.
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U2 - 10.1083/jcb.201006094
DO - 10.1083/jcb.201006094
M3 - Article
C2 - 20974810
AN - SCOPUS:78049520763
SN - 0021-9525
VL - 191
SP - 631
EP - 644
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -