The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.

PloS One
Nicole HarbNoboru Sato

Abstract

Embryonic stem (ES) cells self-renew as coherent colonies in which cells maintain tight cell-cell contact. Although intercellular communications are essential to establish the basis of cell-specific identity, molecular mechanisms underlying intrinsic cell-cell interactions in ES cells at the signaling level remain underexplored. Here we show that endogenous Rho signaling is required for the maintenance of cell-cell contacts in ES cells. siRNA-mediated loss of function experiments demonstrated that Rock, a major effector kinase downstream of Rho, played a key role in the formation of cell-cell junctional assemblies through regulation of myosin II by controlling a myosin light chain phosphatase. Chemical engineering of this signaling axis by a Rock-specific inhibitor revealed that cell-cell adhesion was reversibly controllable and dispensable for self-renewal of mouse ES cells as confirmed by chimera assay. Furthermore, a novel culture system combining a single synthetic matrix, defined medium, and the Rock inhibitor fully warranted human ES cell self-renewal independent of animal-derived matrices, tight cell contacts, or fibroblastic niche-forming cells as determined by teratoma formation assay. These findings demonstrate an ess...Continue Reading

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Feb 28, 2014·Biomacromolecules·Xiaoli ChenMichael J Monteiro
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Methods Mentioned

BETA
GTPases
GTPase
transfection
PCR
transmission electron microscopy
chemical
chip
Protein Assay
fluorescence microscopy

Software Mentioned

iQ5 optical system
Primer Express

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