Document Detail

Heat shock induces apoptosis in human embryonic stem cells but a premature senescence phenotype in their differentiated progeny.
MedLine Citation:
PMID:  22895173     Owner:  NLM     Status:  MEDLINE    
Embryonic stem cells (ESC) are able to self-renew and to differentiate into any cell type. To escape error transmission to future cell progeny, ESC require robust mechanisms to ensure genomic stability. It was stated that stress defense of mouse and human ESC against oxidative stress and irradiation is superior compared with differentiated cells. Here, we investigated heat shock response of human ESC (hESC) and their differentiated progeny. Fibroblast-like cells were generated by spontaneous hESC differentiation via embryoid bodies. Like normal human diploid fibroblasts, these cells have a finite lifespan in culture, undergo replicative senescence and die. We found that sublethal heat shock affected survival of both cell types, but in hESC it induced apoptosis, whereas in differentiated cells it produced cell cycle arrest and premature senescence phenotype. Heat shock survived hESC and differentiated cells restored the properties of initial cells. Heated hESC progeny exhibited pluripotent markers and the capacity to differentiate into the cells of three germ layers. Fibroblast-like cells resisted heat shock, proliferated for a limited number of passages and entered replicative senescence as unheated parental cells. Taken together, these results show for the first time that both hESC and their differentiated derivatives are sensitive to heat shock, but the mechanisms of their stress response are different: hESC undergo apoptosis, whereas differentiated cells under the same conditions exhibit stress-induced premature senescence (SIPS) phenotype. Both cell types that survived sublethal heat shock sustain parental cell properties.
Larisa L Alekseenko; Victoria I Zemelko; Valery V Zenin; Nataly A Pugovkina; Irina V Kozhukharova; Zoya V Kovaleva; Tatiana M Grinchuk; Irina I Fridlyanskaya; Nikolay N Nikolsky
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-16
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  11     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-13     Completed Date:  2013-02-04     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3260-9     Citation Subset:  IM    
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, Russia.
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MeSH Terms
Apoptosis / physiology*
Cell Aging / physiology*
Cell Differentiation / physiology
DNA Primers / genetics
Embryonic Stem Cells / cytology*,  physiology
Fibroblasts / cytology*,  physiology
Flow Cytometry
Fluorescent Antibody Technique
Heat-Shock Proteins / metabolism
Heat-Shock Response / physiology*
Reverse Transcriptase Polymerase Chain Reaction
Reg. No./Substance:
0/DNA Primers; 0/Heat-Shock Proteins; 0/Indoles; 47165-04-8/DAPI

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