title: Maintenance of muscle stem-cell quiescence by microRNA-489.
abstract: Among the key properties that distinguish adult mammalian stem cells from their more differentiated progeny is the ability of stem cells to remain in a quiescent state for prolonged periods of time. However, the molecular pathways for the maintenance of stem-cell quiescence remain elusive. Here we use adult mouse muscle stem cells (satellite cells) as a model system and show that the microRNA (miRNA) pathway is essential for the maintenance of the quiescent state. Satellite cells that lack a functional miRNA pathway spontaneously exit quiescence and enter the cell cycle. We identified quiescence-specific miRNAs in the satellite-cell lineage by microarray analysis. Among these, miRNA-489 (miR-489) is highly expressed in quiescent satellite cells and is quickly downregulated during satellite-cell activation. Further analysis revealed that miR-489 functions as a regulator of satellite-cell quiescence, as it post-transcriptionally suppresses the oncogene Dek, the protein product of which localizes to the more differentiated daughter cell during asymmetric division of satellite cells and promotes the transient proliferative expansion of myogenic progenitors. Our results provide evidence of the miRNA pathway in general, and of a specific miRNA, miR-489, in actively maintaining the quiescent state of an adult stem-cell population.
authors.affiliation: Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Cheung
authors.forename: Navaline L
authors.initials: NL
authors.lastname: Quach
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Charville
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Lidia
authors.initials: L
authors.lastname: Park
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Edalati
authors.forename: Bryan
authors.initials: B
authors.lastname: Yoo
authors.forename: Phuong
authors.initials: P
authors.lastname: Hoang
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C519564:DEK protein, mouse; D004268:DNA-Binding Proteins; C570982:MIRN489 microRNA, mouse; D035683:MicroRNAs; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D013629:Tamoxifen; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases