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Maintenance of muscle stem-cell quiescence by microRNA-489
Open accessAbstract
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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“Satellite cells exist in a quiescence state during life and are activated upon muscle injury to generate new muscle fibers (Bjornson et al., 2012;Cheung et al., 2012).”
From In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming. (2016) · cites this paper as Cheung et al., 2012
In the citing paper
“miR-489 functions to prevent MuSC proliferation by suppressing the oncogene DEK51,90.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [51]
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“This mode of post-transcriptional regulation has emerged as an important aspect in the control of stem cell quiescence, as recently demonstrated in HSCs88 and MuSCs51.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [51]
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“one miRNA, miR-489, is an important regulator of the quiescent state51.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [51]
In the citing paper
“conditional knockout of the miRNA processing factor Dicer triggers spontaneous activation of quiescent MuSCs51.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [51]
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Self-citation
Metadata
- 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.
- Venue
- Nature
- Published
- 2012-02-23
- Volume
- 482
- Issue
- 7386
- Pages
- 524-528
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
- 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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