Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF

We have performed parallel scRNA-seq and snATAC-seq analysis of skeletal muscles subjected to sciatic nerve transection to delineate cell type-specific patterns of gene expression and chromatin accessibility at different time-points post-denervation. This analysis revealed that, unlike muscle injury, denervation leads to the selective activation of specific muscle-resident cell types, such as glial cells and a population of mesenchymal cells marked by the expression of Thy1/CD90. For each time-point post denervation (namely, 2, 5 and 15 days p.d., as well as the non-denervated control (abbreviated as Non-DEN in all figures and tables), 1 wild-type male C5Bl6/N mice at 3 months of age was used for each of the two biological replicates. After sciatic nerve transection, we collected two muscles downstream to the sciatic nerve, the tibialis anterior (TA) and gastrocnemius (GA) muscles. Cells were isolated by Fluorescence-activated cell sorting (FACS) and analyzed using either scRNAseq (for Non-DEN, DEN2d, DEN5d and DEN15d timepoints) or snATAC-seq (for Non-DEN and DEN5d timepoints).