Cited by 461Muscle Physiology and DisordersMicroRNA in disease regulationDevelopmental Biology and Gene Regulation

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Maintenance of muscle stem-cell quiescence by microRNA-489

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Cheung, Tom H., Quach, Navaline L., Charville, Gregory W., Liu, Ling, Park, Lidia, Edalati, Abdolhossein, Yoo, Bryan, Hoang, Phuong, Rando, Thomas A.·2012·Nature

DOI 10.1038/nature10834PMC PMC3292200

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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 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.

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Authors: Cheung, T. H., Quach, N. L., Charville, G. W., Liu, L., Park, L., Edalati, A., Yoo, B., Hoang, P., & Rando, T. A.
Affiliations: Stanford Medicine (US)
VA Palo Alto Health Care System (US)
Corresponding author: Rando, Thomas A.
ORCID: Cheung, Tom H.
Charville, Gregory W.
Liu, Ling
Park, Lidia
Hoang, Phuong
Rando, Thomas A.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-02-23
Volume: 482
Issue: 7386
Pages: 524-528
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature10834
PMC: PMC3292200
OpenAlex: W2074106315
Cited by: 461
References: 25
Citations by year: 2026: 9 · 2025: 22 · 2024: 20 · 2023: 24 · 2022: 23 · 2021: 27 · 2020: 40 · 2019: 40 · 2018: 25 · 2017: 45 · 2016: 36 · 2015: 53 · 2014: 40 · 2013: 36 · 2012: 21
FWCI: 19.27
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Glenn Foundation for Medical Research
National Institutes of Health (DP1OD000392)
National Institute on Aging (R01 AG23806, R37AG023806, R01AG023806, F30AG035521, P01AG036695)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR062185, R01AR056849)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: miR-489, microRNA, muscle stem cells, satellite cells, stem cell quiescence, DEK, cell cycle re-entry, asymmetric cell division, myogenic progenitor cells, post-transcriptional regulation, stem cell self-renewal
MeSH terms: Poly-ADP-Ribose Binding Proteins, Animals, Cell Cycle, Cell Differentiation, Cell Survival, DNA-Binding Proteins, Gene Expression Regulation, Mice, Inbred C57BL, Tamoxifen, Transcription, Genetic, Oncogene Proteins, Cell Lineage, Oligonucleotide Array Sequence Analysis, Myoblasts, Satellite Cells, Skeletal Muscle, MicroRNAs, Ribonuclease III, Mice, DEAD-box RNA Helicases, Gene Knockdown Techniques

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