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The aged niche disrupts muscle stem cell quiescence.
- Source :
-
Nature [Nature] 2012 Oct 18; Vol. 490 (7420), pp. 355-60. Date of Electronic Publication: 2012 Sep 26. - Publication Year :
- 2012
-
Abstract
- The niche is a conserved regulator of stem cell quiescence and function. During ageing, stem cell function declines. To what extent and by what means age-related changes within the niche contribute to this phenomenon are unknown. Here we demonstrate that the aged muscle stem cell niche, the muscle fibre, expresses Fgf2 under homeostatic conditions, driving a subset of satellite cells to break quiescence and lose their self-renewing capacity. We show in mice that relatively dormant aged satellite cells robustly express sprouty 1 (Spry1), an inhibitor of fibroblast growth factor (FGF) signalling. Increasing FGF signalling in aged satellite cells under homeostatic conditions by removing Spry1 results in the loss of quiescence, satellite cell depletion and diminished regenerative capacity. Conversely, reducing niche-derived FGF activity through inhibition of Fgfr1 signalling or overexpression of Spry1 in satellite cells prevents their depletion. These experiments identify an age-dependent change in the stem cell niche that directly influences stem cell quiescence and function.
- Subjects :
- Adaptor Proteins, Signal Transducing
Animals
Cell Count
Cell Differentiation
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p27 metabolism
Fibroblast Growth Factor 2 genetics
Fibroblast Growth Factor 2 metabolism
Flow Cytometry
Homeostasis
Membrane Proteins metabolism
Mice
Mice, Inbred C57BL
Muscle, Skeletal cytology
PAX7 Transcription Factor metabolism
Phosphoproteins metabolism
Satellite Cells, Skeletal Muscle metabolism
Satellite Cells, Skeletal Muscle transplantation
Signal Transduction
Time Factors
Aging physiology
Cell Cycle
Muscle Cells cytology
Satellite Cells, Skeletal Muscle cytology
Stem Cell Niche physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 490
- Issue :
- 7420
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 23023126
- Full Text :
- https://doi.org/10.1038/nature11438