Skeletal muscle maintenance depends on motor innervation at neuromuscular junctions (NMJs). NMJs degeneration is a prominent aspect of denervation, aging, pathological conditions, such as Amyotrophic Lateral Sclerosis (ALS). All these conditions cause weakness, paralysis and atrophy of skeletal muscles. The precise molecular mechanisms and roles of muscle-resident cells remain largely unknown.
Therefore, a better understanding of the cellular signaling pathways in muscle-resident cells during traumatic or pathological denervation is critical for developing better therapies against neurogenic muscle atrophy and degenerative diseases. We used RNAseq analysis to compare transcriptomes of skeletal muscle, FAPs and SCs isolated from denervated muscle in order to identify the transcriptional signatures that underlie neurogenic muscle atrophy and to determinate the roles in this process of muscle-resident cells.
These advances in gene expression profiling could lead to discover new potential targets to counteract the effect of muscle denervation and ALS.
The fundamental role of SC in rebuilding new muscle fibers and reconstituting muscle function following damage is now well established. On the other hand, their participation in the neuron-muscle interaction remains unclear.
In neuromuscular disorders, such as Amyotrophic Lateral Sclerosis (ALS), a disruption of the neuron-muscle interaction leads to muscle denervation, muscle atrophy and loss of function, with devastating consequences to the patient¿s health and often with invariably fatal outcome.
We recently observed that SC are sensitive to muscle denervation and activate an alternative pro-neurotrophic gene expression program uncoupled with the canonical activation of the myogenic program.
The opportunity to identify molecular mechanisms and molecular mediators of muscle satellite cells and motoneurons cross-talk is decisive to figure out the role of these cells during neurogenic muscle atrophy and to identify molecular mediators to promote muscle reinnervation and counteract the denervation effects.
Successful achievement of these objectives will expand the functional repertoire of SC by attributing to them a key function in skeletal muscle innervation. This would pave the way for new research studies on the role of SCs in the maintenance of nerve-muscle interaction and ultimately could be translated into clinical applications.