The aged niche disrupts muscle stem cell quiescence

By Joe V. Chakkalakal, Kieran M. Jones, M. A. Basson, A. Brack. Nature, 2012

778 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c9d0041233d1dd2f6e688f81e11b598547d3eeb0

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Citations in the corpus

The hallmarks of aging. (2013, background): “tive capacity, whereas suppression of this signaling pathway rescues these defects (Chakkalakal et al., 2012).”
Satellite Cells and Skeletal Muscle Regeneration (2015, positive): “Aged muscle fibers were shown to express more FGF2, which activates satellite cells and decreases their self-renewal potential (53).”
FGF/FGFR signaling in health and disease (2020, methodology): “Thus, blockade of FGF2/FGFR1 signaling might be a new therapeutic method to recover the regeneration capacity of skeletal muscles during aging.(408) The expression of FGF2 is found to be increased during the muscle regeneration,(398) and exogenous FGF2 could promote muscle regeneration in dystrophic”
In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming (2016, positive): “The age-associated loss of muscle mass during aging results from a decline in the regenerative capacity of muscle stem cells, also known as satellite cells (Chakkalakal et al., 2012; Cosgrove et al., 2014).”