Publication Date:
2012-10-02
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605795/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605795/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chakkalakal, Joe V -- Jones, Kieran M -- Basson, M Albert -- Brack, Andrew S -- 091475/Wellcome Trust/United Kingdom -- BB/F017626/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- R01 AR060868/AR/NIAMS NIH HHS/ -- R01 AR061002/AR/NIAMS NIH HHS/ -- WT091475/Wellcome Trust/United Kingdom -- England -- Nature. 2012 Oct 18;490(7420):355-60. doi: 10.1038/nature11438. Epub 2012 Sep 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23023126" target="_blank"〉PubMed〈/a〉
Keywords:
Adaptor Proteins, Signal Transducing
;
Aging/*physiology
;
Animals
;
Cell Aging
;
Cell Count
;
*Cell Cycle
;
Cell Differentiation
;
Cyclin-Dependent Kinase Inhibitor p27/metabolism
;
Fibroblast Growth Factor 2/genetics/metabolism
;
Flow Cytometry
;
Homeostasis
;
Membrane Proteins/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Muscle Cells/*cytology
;
Muscle, Skeletal/cytology
;
PAX7 Transcription Factor/metabolism
;
Phosphoproteins/metabolism
;
Satellite Cells, Skeletal Muscle/*cytology/metabolism/transplantation
;
Signal Transduction
;
Stem Cell Niche/*physiology
;
Time Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
