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

<h4>Background</h4>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 interact...

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Autores principales:	Nicole Harb, Trevor K Archer, Noboru Sato
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bf3348547fa0475f8b9984de20191ba8
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spelling	oai:doaj.org-article:bf3348547fa0475f8b9984de20191ba82021-12-02T20:12:19ZThe Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.1932-620310.1371/journal.pone.0003001https://doaj.org/article/bf3348547fa0475f8b9984de20191ba82008-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18714354/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>These findings demonstrate an essential role of the Rho-Rock-Myosin signaling axis for the regulation of basic cell-cell communications in both mouse and human ES cells, and would contribute to advance in medically compatible xeno-free environments for human pluripotent stem cells.Nicole HarbTrevor K ArcherNoboru SatoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 8, p e3001 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Harb Trevor K Archer Noboru Sato The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>These findings demonstrate an essential role of the Rho-Rock-Myosin signaling axis for the regulation of basic cell-cell communications in both mouse and human ES cells, and would contribute to advance in medically compatible xeno-free environments for human pluripotent stem cells.
format	article
author	Nicole Harb Trevor K Archer Noboru Sato
author_facet	Nicole Harb Trevor K Archer Noboru Sato
author_sort	Nicole Harb
title	The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
title_short	The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
title_full	The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
title_fullStr	The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
title_full_unstemmed	The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
title_sort	rho-rock-myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/bf3348547fa0475f8b9984de20191ba8
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The Rho-Rock-Myosin signaling axis determines cell-cell integrity of self-renewing pluripotent stem cells.

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