Document Detail

Identification of a novel microRNA that regulates the proliferation and differentiation in muscle side population cells.
MedLine Citation:
PMID:  22541023     Owner:  NLM     Status:  MEDLINE    
Muscle satellite cells are largely responsible for skeletal muscle regeneration following injury. Side population (SP) cells, which are thought to be muscle stem cells, also contribute to muscle regeneration. SP cells exhibit high mesenchymal potential, and are a possible cell source for therapy of muscular dystrophy. However, the mechanism by which muscle SP cells are committed to differentiation is poorly understood. microRNAs (miRNAs) play key roles in modulating a variety of cellular processes through repression of their mRNA targets. In skeletal muscle, miRNAs are known to be involved in myoblast proliferation and differentiation. To investigate mechanisms of SP cell regulation, we profiled miRNA expression in SP cells and main population (MP) cells in muscles using quantitative real-time polymerase chain reaction-based expression assays. We identified a set of miRNAs that was highly expressed in SP cells as compared with MP cells. One miRNA, miR-128a, was elevated in expression in SP cells, but decreased in expression during continued culture in vitro. Overexpression of miR-128a in SP cells resulted in inhibited cell proliferation. The differentiation potential of SP cells was also decreased when miR-128a was overexpressed. MiR-128a was found to regulate the target genes involved in the regulation of adipogenic-, osteogenic- and myogenic genes that include: PPARγ, Runx1, and Pax3. Overexpression of miR-128a suppressed the activity of a luciferase reporter fused to the 3'-untranslated region of each gene. These results demonstrate that miR-128a contributes to the maintenance of the quiescent state, and it regulates cellular differentiation by repressing individual genes in SP cells.
Norio Motohashi; Matthew S Alexander; Juan Carlos Casar; Louis M Kunkel
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Publication Detail:
Type:  Journal Article     Date:  2012-06-12
Journal Detail:
Title:  Stem cells and development     Volume:  21     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-18     Completed Date:  2013-03-26     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3031-43     Citation Subset:  IM    
Program in Genomics, Department of Pediatrics, Children's Hospital Boston, Boston, Massachusetts, USA.
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MeSH Terms
Adipogenesis / genetics
Cell Compartmentation / genetics
Cell Differentiation / genetics*
Cell Proliferation
Cell Size
Core Binding Factor Alpha 2 Subunit / genetics,  metabolism
Gene Expression Regulation*
Mice, Inbred C57BL
MicroRNAs / genetics,  metabolism*
Muscle Development / genetics
Muscles / cytology*
Osteogenesis / genetics
PPAR gamma / genetics,  metabolism
Paired Box Transcription Factors / genetics,  metabolism
Side-Population Cells / cytology*,  metabolism*
Grant Support
Reg. No./Substance:
0/Core Binding Factor Alpha 2 Subunit; 0/MicroRNAs; 0/Mirn128 microRNA, mouse; 0/PPAR gamma; 0/Paired Box Transcription Factors; 0/Runx1 protein, mouse; 138016-91-8/Pax3 protein, mouse

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