| First Author | Nicoletti C | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 7 | Pages | 107114 |
| PubMed ID | 37416457 | Mgi Jnum | J:337910 |
| Mgi Id | MGI:7508801 | Doi | 10.1016/j.isci.2023.107114 |
| Citation | Nicoletti C, et al. (2023) Muscle denervation promotes functional interactions between glial and mesenchymal cells through NGFR and NGF. iScience 26(7):107114 |
| abstractText | We performed scRNA-seq/snATAC-seq of skeletal muscles post sciatic nerve transection to delineate cell type-specific patterns of gene expression/chromatin accessibility at different time points post-denervation. Unlike myotrauma, denervation selectively activates glial cells and Thy1/CD90-expressing mesenchymal cells. Glial cells expressed Ngf receptor (Ngfr) and were located near neuromuscular junctions (NMJs), close to Thy1/CD90-expressing cells, which provided the main cellular source of NGF post-denervation. Functional communication between these cells was mediated by NGF/NGFR, as either recombinant NGF or co-culture with Thy1/CD90-expressing cells could increase glial cell number ex vivo. Pseudo-time analysis in glial cells revealed an initial bifurcation into processes related to either cellular de-differentiation/commitment to specialized cell types (e.g., Schwann cells), or failure to promote nerve regeneration, leading to extracellular matrix remodeling toward fibrosis. Thus, interactions between denervation-activated Thy1/CD90-expressing and glial cells represent an early abortive process toward NMJs repair, ensued by the conversion of denervated muscles into an environment hostile for NMJ repair. |
