Document Detail


Adult stem cells exhibit global suppression of RNA polymerase II serine-2 phosphorylation.
MedLine Citation:
PMID:  20641035     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adult stem cells, which are characterized by their capacity for self-renewal and differentiation, participate in tissue homeostasis and response to injury. They are thought to enter a state of relative quiescence, known as reversible cell cycle arrest, but the underlying molecular mechanisms remain poorly characterized. Previous data from our laboratory has shown that housekeeping gene expression is downregulated in melanocyte stem cells (MelSCs), suggesting a global suppression of mRNA transcription. We now show, using antibodies against specific phosphorylated forms of RNA polymerase II (RNApII), that adult MelSCs do not undergo productive mRNA transcription elongation, while RNApII is activated and initialized, ready to synthesize mRNA upon stimulation, and that the RNApII kinase CDK9 is absent in adult MelSCs. Interestingly, other adult stem cells also, including keratinocyte, muscle, spermatogonia, and hematopoietic stem cells, showed a similar absence of RNApII phosphorylation. Although it is difficult to show the functional significance of this observation in vivo, CDK9 inhibition resulted in enhanced survival of cells that are deprived from survival factors. We conclude that the absence of productive mRNA transcription is an early, specific, and conserved characteristic of adult stem cells. Downregulation of mRNA transcription may lead to decreased rates of metabolism, and protection from cellular and genetic damage. Screening heterogeneous tissues, including tumors, for transcriptionally quiescent cells may result in the identification of cells with stem cell-like phenotypes.
Authors:
Rasmus Freter; Masatake Osawa; Shin-Ichi Nishikawa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cells (Dayton, Ohio)     Volume:  28     ISSN:  1549-4918     ISO Abbreviation:  Stem Cells     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-30     Completed Date:  2010-11-08     Revised Date:  2012-06-20    
Medline Journal Info:
Nlm Unique ID:  9304532     Medline TA:  Stem Cells     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1571-80     Citation Subset:  IM    
Affiliation:
Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. rasmus.freter@ludwig.ox.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adult Stem Cells / enzymology*
Animals
Cell Aging* / genetics
Cell Differentiation
Cell Proliferation
Cyclin-Dependent Kinase 9 / genetics,  metabolism
Down-Regulation
Genotype
Male
Melanocytes / enzymology*
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Transgenic
Mutation
NIH 3T3 Cells
Phenotype
Phosphorylation
Promoter Regions, Genetic
Protein Processing, Post-Translational*
Proteins / genetics,  metabolism
Proto-Oncogene Proteins c-kit / metabolism
RNA Polymerase II / metabolism*
Serine
Signal Transduction
Stem Cell Factor / metabolism
Time Factors
Transcription, Genetic
Transfection
Chemical
Reg. No./Substance:
0/Gt(ROSA)26Sor protein, mouse; 0/Proteins; 0/Stem Cell Factor; 56-45-1/Serine; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 2.7.11.22/Cdk9 protein, mouse; EC 2.7.11.22/Cyclin-Dependent Kinase 9; EC 2.7.7.-/RNA Polymerase II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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