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PMID: 20682449 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Actin-myosin contractility is responsible for the reduced viability of dissociated human embryonic stem cells.

Cell stem cell ·Vol. 7 ·No. 2 ·2010-08-06 ·Pages 240-8

Chen G, Hou Z, Gulbranson DR, Thomson JA

Abstract

Human ESCs are the pluripotent precursor of the three embryonic germ layers. Human ESCs exhibit basal-apical polarity, junctional complexes, integrin-dependent matrix adhesion, and E-cadherin-dependent cell-cell adhesion, all characteristics shared by the epiblast epithelium of the intact mammalian embryo. After disruption of epithelial structures, programmed cell death is commonly observed. If individualized human ESCs are prevented from reattaching and forming colonies, their viability is significantly reduced. Here, we show that actin-myosin contraction is a critical effector of the cell death response to human ESC dissociation. Inhibition of myosin heavy chain ATPase, downregulation of myosin heavy chain, and downregulation of myosin light chain all increase survival and cloning efficiency of individualized human ESCs. ROCK inhibition decreases phosphorylation of myosin light chain, suggesting that inhibition of actin-myosin contraction is also the mechanism through which ROCK inhibitors increase cloning efficiency of human ESCs.

MeSH Terms
Actin Cytoskeleton/drug effects,metabolism Actins/metabolism Cell Communication/drug effects Cell Death/drug effects Cell Surface Extensions/drug effects,metabolism Cell Survival/drug effects Clone Cells Embryonic Stem Cells/cytology,drug effects,enzymology,metabolism Gene Knockdown Techniques Heterocyclic Compounds, 4 or More Rings/pharmacology Humans Molecular Motor Proteins/metabolism Myosin Heavy Chains/metabolism Myosin Light Chains/antagonists & inhibitors,metabolism Myosins/metabolism Phosphorylation/drug effects rho-Associated Kinases/metabolism
Chemicals
Actins Heterocyclic Compounds, 4 or More Rings MYH9 protein, human Molecular Motor Proteins Myosin Light Chains blebbistatin rho-Associated Kinases Myosin Heavy Chains Myosins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chen Guokai
Morgridge Institute for Research, Madison, WI 53707-7365, USA.
Hou Zhonggang
Gulbranson Daniel R
Thomson James A
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Article Info
Journal
Cell stem cell
Abbr.
Cell Stem Cell
ISSN
1875-9777
DOI
10.1016/j.stem.2010.06.017
Published
2010-08-06
Pages
240-8
Language
English
Region
United States
NLM ID
101311472
PMCID
PMC2916864
Subset
IM
Grants
NIEHS NIH HHS · U01 ES017166 · United States
NIEHS NIH HHS · U01 ES017166-02 · United States
NIEHS NIH HHS · U01ES017166 · United States
NCRR NIH HHS · RR-05-19 · United States
Corrections
CommentIn
PMID: 20682437
External Links
PubMed source DOI: 10.1016/j.stem.2010.06.017 PMC Full Text View journal details
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