The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration
dc.contributor.author | Zhao, XF | |
dc.contributor.author | Huffman, LD | |
dc.contributor.author | Hafner, H | |
dc.contributor.author | Athaiya, M | |
dc.contributor.author | Finneran, MC | |
dc.contributor.author | Kalinski, AL | |
dc.contributor.author | Kohen, R | |
dc.contributor.author | Flynn, C | |
dc.contributor.author | Passino, R | |
dc.contributor.author | Johnson, CN | |
dc.contributor.author | Kohrman, D | |
dc.contributor.author | Kawaguchi, R | |
dc.contributor.author | Yang, LJS | |
dc.contributor.author | Twiss, JL | |
dc.contributor.author | Geschwind, DH | |
dc.contributor.author | Corfas, G | |
dc.contributor.author | Giger, RJ | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-05-21T15:14:28Z | |
dc.date.available | 2024-05-21T15:14:28Z | |
dc.date.issued | 2022-12-01 | |
dc.identifier.issn | 2050-084X | |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/36515985 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/193167 | en |
dc.description.abstract | 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 naïve mouse sciatic nerve, peripheral blood mono-nuclear 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 naïve 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/. | |
dc.format.medium | Electronic | |
dc.language | eng | |
dc.publisher | eLife | |
dc.relation.haspart | ARTN e80881 | |
dc.rights | Licence for published version: Creative Commons Attribution 4.0 International | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Wallerian degeneration | |
dc.subject | immunology | |
dc.subject | inflammation | |
dc.subject | mouse | |
dc.subject | neuroscience | |
dc.subject | parabiosis | |
dc.subject | regeneration | |
dc.subject | sciatic nerve | |
dc.subject | single-cell RNA seq | |
dc.subject | Mice | |
dc.subject | Animals | |
dc.subject | Wallerian Degeneration | |
dc.subject | Leukocytes, Mononuclear | |
dc.subject | Sciatic Nerve | |
dc.subject | Nerve Degeneration | |
dc.subject | Nerve Crush | |
dc.subject | Peripheral Nerve Injuries | |
dc.subject | Nerve Regeneration | |
dc.subject | Cytoskeletal Proteins | |
dc.subject | Armadillo Domain Proteins | |
dc.title | The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration | |
dc.type | Article | |
dc.identifier.pmid | 36515985 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/193167/2/The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and re.pdf | |
dc.identifier.doi | 10.7554/ELIFE.80881 | |
dc.identifier.doi | https://dx.doi.org/10.7302/22812 | |
dc.identifier.source | eLife | |
dc.description.version | Published version | |
dc.date.updated | 2024-05-21T15:14:16Z | |
dc.identifier.orcid | 0000-0002-7574-7163 | |
dc.identifier.orcid | 0000-0002-7779-086X | |
dc.identifier.orcid | 0000-0001-7611-0810 | |
dc.identifier.orcid | 0000-0001-5811-7269 | |
dc.identifier.orcid | 0000-0003-3955-7394 | |
dc.identifier.orcid | 0000-0001-6888-6889 | |
dc.identifier.orcid | 0000-0001-7875-6682 | |
dc.identifier.orcid | 0000-0003-2896-3450 | |
dc.identifier.orcid | 0000-0001-5412-9473 | |
dc.identifier.orcid | 0000-0002-2926-3336 | |
dc.description.filedescription | Description of The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and re.pdf : Published version | |
dc.identifier.volume | 11 | |
dc.identifier.startpage | e80881 | |
dc.identifier.name-orcid | Zhao, XF; 0000-0002-7574-7163 | |
dc.identifier.name-orcid | Huffman, LD; 0000-0002-7779-086X | |
dc.identifier.name-orcid | Hafner, H | |
dc.identifier.name-orcid | Athaiya, M | |
dc.identifier.name-orcid | Finneran, MC | |
dc.identifier.name-orcid | Kalinski, AL; 0000-0001-7611-0810 | |
dc.identifier.name-orcid | Kohen, R | |
dc.identifier.name-orcid | Flynn, C; 0000-0001-5811-7269 | |
dc.identifier.name-orcid | Passino, R | |
dc.identifier.name-orcid | Johnson, CN; 0000-0003-3955-7394 | |
dc.identifier.name-orcid | Kohrman, D; 0000-0001-6888-6889 | |
dc.identifier.name-orcid | Kawaguchi, R | |
dc.identifier.name-orcid | Yang, LJS | |
dc.identifier.name-orcid | Twiss, JL; 0000-0001-7875-6682 | |
dc.identifier.name-orcid | Geschwind, DH; 0000-0003-2896-3450 | |
dc.identifier.name-orcid | Corfas, G; 0000-0001-5412-9473 | |
dc.identifier.name-orcid | Giger, RJ; 0000-0002-2926-3336 | |
dc.working.doi | 10.7302/22812 | en |
dc.owningcollname | Molecular and Behavioral Neurosciences Institute |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.