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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 time1,2. 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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS MEF2C SHAPES THE MICROTRANSCRIPTOME DURING DIFFERENTIATION OF SKELETAL

MUSCLES Article Open access 10 February 2021 TRANSLATIONAL CONTROL BY DHX36 BINDING TO 5′UTR G-QUADRUPLEX IS ESSENTIAL FOR MUSCLE STEM-CELL REGENERATIVE FUNCTIONS Article Open access 19

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(2001) Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the members of the Rando laboratory for comments and discussions. We thank B. Olwin for providing the

syndecan 4 antibody. This work was supported by the Glenn Foundation for Medical Research and by grants from the National Institutes of Health (NIH) (P01 AG036695, R01 AG23806 (R37 MERIT

Award), R01 AR062185 and DP1 OD000392 (an NIH Director's Pioneer Award)) and the Department of Veterans Affairs (Merit Review) to T.A.R. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Paul F. Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, 94305, California, USA Tom H. Cheung, Navaline L. Quach, Gregory W. Charville, Ling

Liu, Lidia Park, Abdolhossein Edalati, Bryan Yoo, Phuong Hoang & Thomas A. Rando * Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford,

94305, California, USA Tom H. Cheung, Navaline L. Quach, Gregory W. Charville, Ling Liu, Lidia Park, Abdolhossein Edalati, Bryan Yoo, Phuong Hoang & Thomas A. Rando * Department of

Developmental Biology, Stanford University School of Medicine, Stanford, 94305, California, USA Gregory W. Charville * Neurology Service, Veterans Affairs Palo Alto Health Care System, Palo

Alto, 94304, California, USA Thomas A. Rando * Rehabiliitation Research and Development Center of Excellence, Veterans Affairs Palo Alto Health Care System, Palo Alto, 94304, California, USA

Thomas A. Rando Authors * Tom H. Cheung View author publications You can also search for this author inPubMed Google Scholar * Navaline L. Quach View author publications You can also search

for this author inPubMed Google Scholar * Gregory W. Charville View author publications You can also search for this author inPubMed Google Scholar * Ling Liu View author publications You

can also search for this author inPubMed Google Scholar * Lidia Park View author publications You can also search for this author inPubMed Google Scholar * Abdolhossein Edalati View author

publications You can also search for this author inPubMed Google Scholar * Bryan Yoo View author publications You can also search for this author inPubMed Google Scholar * Phuong Hoang View

author publications You can also search for this author inPubMed Google Scholar * Thomas A. Rando View author publications You can also search for this author inPubMed Google Scholar

CONTRIBUTIONS T.H.C. and T.A.R. conceived the study. T.H.C., N.L.Q., G.W.C., L.L. and T.A.R. designed the experiments. T.H.C., B.Y. and L.L. performed all FACS analyses. T.H.C., N.L.Q.,

G.W.C., L.P., A.E., B.Y. and P.H. performed the experiments and analysed the experimental data. T.H.C. and T.A.R. wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Thomas A.

Rando. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY INFORMATION This file contains Supplementary

Figures 1-14 with legends and Supplementary Table 1. (PDF 2023 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR

FIG. 4 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Cheung, T., Quach, N., Charville, G. _et al._ Maintenance of muscle stem-cell quiescence by

microRNA-489. _Nature_ 482, 524–528 (2012). https://doi.org/10.1038/nature10834 Download citation * Received: 16 January 2011 * Accepted: 05 January 2012 * Published: 23 February 2012 *

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