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

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-cateni...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of cell biology 2010-11, Vol.191 (3), p.631-644
Main Authors: 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
Format: Article
Language:English
Subjects:
Antibodies
Biochemistry
Cadherins
Cadherins - metabolism
Catenins - metabolism
Cell lines
Cells, Cultured
Cellular biology
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Epithelial cells
Humans
Nonmuscle Myosin Type IIA - metabolism
Physiological regulation
Pluripotent stem cells
Protein isoforms
Proteins
Signal Transduction
Somatic cells
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201006094