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Elife. 2015 Aug 27;4. doi: 10.7554/eLife.09221.

Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions.

Author information

1
Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, United States.
2
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, United States.

Abstract

Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). Multiple mechanisms contribute to NMJ repair and maintenance; however muscle stem cells (satellite cells, SCs), are deemed to have little impact on these processes. Therefore, the applicability of SC studies to attenuate muscle loss due to NMJ deterioration as observed in neuromuscular diseases and aging is ambiguous. We employed mice with an inducible Cre, and conditionally expressed DTA to deplete or GFP to track SCs. We found SC depletion exacerbated muscle atrophy and type transitions connected to neuromuscular disruption. Also, elevated fibrosis and further declines in force generation were specific to SC depletion and neuromuscular disruption. Fate analysis revealed SC activity near regenerating NMJs. Moreover, SC depletion aggravated deficits in reinnervation and post-synaptic morphology at regenerating NMJs. Therefore, our results propose a mechanism whereby further NMJ and skeletal muscle decline ensues upon SC depletion and neuromuscular disruption.

KEYWORDS:

aging; cell biology; denervation; developmental biology; motor neuron; mouse; sarcopenia; satellite cell; stem cells; synapse

PMID:
26312504
PMCID:
PMC4579298
DOI:
10.7554/eLife.09221
[Indexed for MEDLINE]
Free PMC Article

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