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.
Highlights
Skeletal muscle is composed of long multinucleated cells, muscle fibers, which function as primary effectors for force production and contribute to the regulation of whole body metabolism
In doing so we found that upon neuromuscular junction (NMJ) disruption: i) satellite cells (SCs) depletion exacerbates myofiber atrophy and type transitions; ii) SC depletion leads to elevated fibrosis and declines in muscle force generating capacity; iii) SC-derived contributions prevail in the vicinity of NMJs; and iv) SC depletion leads to deficits in skeletal muscle reinnervation, reductions in post-synaptic morphology and loss of post-synaptic myonuclei
Through these findings we propose a cellular mechanism whereby SCs contribute to the regeneration of NMJs and skeletal muscle maintenance upon neuromuscular disruption
Summary
Skeletal muscle is composed of long multinucleated cells, muscle fibers (myofibers), which function as primary effectors for force production and contribute to the regulation of whole body metabolism. Primarily a post-mitotic tissue, adult skeletal muscle possesses a remarkable capacity for regeneration This capacity is endowed by a population of resident stem cells, satellite cells (SCs), identified by the expression of the paired box transcription factor Pax (Tajbakhsh, 2009; Brack and Rando, 2012; Yin et al, 2013). Since the initial identification of SCs over 50 years ago, many studies have examined roles for these cells in a plethora of distinct models of skeletal muscle injury, adaptability and disease (Mauro, 1961; Relaix and Zammit, 2012). Depletion studies have revealed roles for Pax7+ SCs in late stages of experimentally induced skeletal muscle hypertrophy (Fry et al, 2014)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
