| First Author | Zhao XF | Year | 2022 |
| Journal | Elife | Volume | 11 |
| PubMed ID | 36515985 | Mgi Jnum | J:380531 |
| Mgi Id | MGI:8279139 | Doi | 10.7554/eLife.80881 |
| Citation | Zhao XF, et al. (2022) The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration. Elife 11 |
| abstractText | Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of naive mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1 day, 3 days, and 7 days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with a high glycolytic flux dominate the early injury response and rapidly give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood-nerve barrier, proliferation of endoneurial and perineurial stromal cells, and entry of opsonizing serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1(-/-) mice, in which Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1(-/-) mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naive and injured PNS and report on hundreds of ligand-receptor interactions. Our longitudinal analysis represents a new resource for neural tissue regeneration, reveals location- specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/. |
