Adult Stem Cells Exhibit Global Suppression of RNA Polymerase II Serine‐2 Phosphorylation

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...

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Vydáno v:Stem cells (Dayton, Ohio) Ročník 28; číslo 9; s. 1571 - 1580
Hlavní autoři: Freter, Rasmus, Osawa, Masatake, Nishikawa, Shin‐Ichi
Médium: Journal Article
Jazyk:angličtina
Vydáno: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2010
Témata:
Adult stem cells
Adult Stem Cells - enzymology
Animals
Cell Differentiation
Cell Proliferation
Cellular Senescence - genetics
Cyclin-Dependent Kinase 9 - genetics
Cyclin-Dependent Kinase 9 - metabolism
Cyclin‐dependent kinase 9
Down-Regulation
Genotype
Male
Melanocytes - enzymology
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Transgenic
mRNA transcription
Mutation
NIH 3T3 Cells
Phenotype
Phosphorylation
Promoter Regions, Genetic
Protein Processing, Post-Translational
Proteins - genetics
Proteins - metabolism
Proto-Oncogene Proteins c-kit - metabolism
Quiescence
RNA Polymerase II - metabolism
RNA, Untranslated
Serine
Signal Transduction
Stem Cell Factor - metabolism
Time Factors
Transcription, Genetic
Transfection
ISSN:1066-5099, 1549-4918, 1549-4918
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Shrnutí: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. STEM CELLS 2010; 28:1571–1580.
Bibliografie:First published online in STEM CELLS
Author contributions: R.F.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; M.O.: conception and design, final approval of manuscript; S.‐I.N.: conception and design, data analysis and interpretation, manuscript writing, final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
July 16, 2010.
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ISSN:1066-5099
1549-4918
1549-4918
DOI:10.1002/stem.476