|Adult stem cells exhibit global suppression of RNA polymerase II serine-2 phosphorylation.|
|PMID: 20641035 Owner: NLM Status: MEDLINE|
|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.|
|Rasmus Freter; Masatake Osawa; Shin-Ichi Nishikawa|
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|Type: Journal Article; Research Support, Non-U.S. Gov't|
|Title: Stem cells (Dayton, Ohio) Volume: 28 ISSN: 1549-4918 ISO Abbreviation: Stem Cells Publication Date: 2010 Sep|
|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|
|Languages: eng Pagination: 1571-80 Citation Subset: IM|
|Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom. email@example.com|
|APA/MLA Format Download EndNote Download BibTex|
Adult Stem Cells
Cell Aging* / genetics
Cyclin-Dependent Kinase 9 / genetics, metabolism
Melanocytes / enzymology*
Mice, Inbred C57BL
Mice, Inbred ICR
NIH 3T3 Cells
Promoter Regions, Genetic
Protein Processing, Post-Translational*
Proteins / genetics, metabolism
Proto-Oncogene Proteins c-kit / metabolism
RNA Polymerase II / metabolism*
Stem Cell Factor / metabolism
|0/Gt(ROSA)26Sor protein, mouse; 0/Proteins; 0/Stem Cell Factor; 56-45-1/Serine; EC 184.108.40.206/Proto-Oncogene Proteins c-kit; EC 220.127.116.11/Cdk9 protein, mouse; EC 18.104.22.168/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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