{"doi":"10.7554/elife.80881","title":"The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration","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 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 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/ .","journal":"eLife","year":2022,"id":234798,"datarank":1.6758896505405263,"base_score":4.5217885770490405,"endowment":4.5217885770490405,"self_citation_contribution":0.6782682865573562,"citation_network_contribution":0.9976213639831701,"self_endowment_contribution":0.6782682865573562,"citer_contribution":0.9976213639831701,"corpus_percentile":87.52997601918466,"corpus_rank":1613,"citation_count":91,"citer_count":78,"citers_with_citation_signal":49,"citers_with_endowment":49,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.8494,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE198582"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":41.6667,"fair_percentile":54.173035768878016,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253504,"name":"Lucas D. Huffman","orcid":"0000-0002-7779-086X","position":1,"is_corresponding":false},{"id":253508,"name":"Hannah Hafner","orcid":"0000-0002-4908-4132","position":2,"is_corresponding":false},{"id":851325,"name":"Mitre Athaiya","orcid":"0000-0002-7526-4663","position":3,"is_corresponding":false},{"id":430550,"name":"Matthew C. Finneran","orcid":"0000-0002-6742-206X","position":4,"is_corresponding":false},{"id":253503,"name":"Ashley L. Kalinski","orcid":"0000-0001-7611-0810","position":5,"is_corresponding":false},{"id":253506,"name":"Rafi Kohen","orcid":"0000-0001-5651-712X","position":6,"is_corresponding":false},{"id":564858,"name":"Corey Flynn","orcid":"0000-0001-5811-7269","position":7,"is_corresponding":false},{"id":253507,"name":"Ryan Passino","orcid":"0000-0002-7485-1313","position":8,"is_corresponding":false},{"id":58634,"name":"Craig N. Johnson","orcid":"0000-0003-3955-7394","position":9,"is_corresponding":false},{"id":752454,"name":"David C. Kohrman","orcid":"0000-0001-6888-6889","position":10,"is_corresponding":false},{"id":226817,"name":"Riki Kawaguchi","orcid":"0000-0002-2489-4825","position":11,"is_corresponding":false},{"id":851326,"name":"Lynda J.‐S. Yang","orcid":"0000-0001-7474-8036","position":12,"is_corresponding":false},{"id":331997,"name":"Jeffery L. Twiss","orcid":"0000-0001-7875-6682","position":13,"is_corresponding":false},{"id":21398,"name":"Daniel H. Geschwind","orcid":"0000-0003-2896-3450","position":14,"is_corresponding":false},{"id":325055,"name":"Gabriel Corfas","orcid":"0000-0001-5412-9473","position":15,"is_corresponding":false},{"id":253512,"name":"Roman J. Giger","orcid":"0000-0002-2926-3336","position":16,"is_corresponding":false},{"id":564859,"name":"Xiaofeng Zhao","orcid":"0000-0002-7574-7163","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":null,"created_at":"2026-07-19T00:21:42.662304Z","pmid":"36515985","pmcid":"PMC9829412","fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":50.0,"fair_a":75.0,"fair_i":0.0,"fair_r":25.0,"fair_zscore":0.2857,"fair_rationale":{"fair_score":41.67,"has_llm":true,"taxonomy_version":"fair_taxonomy_v5","dimensions":{"F":{"name":"Findable","score":50.0,"criteria":[{"key":"f_dataset_pid","label":"Persistent identifier for the data","kind":"llm","weight":2.0,"fraction":0.5,"verdict":"partial","evidence":"To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/ .","grounded":true,"rationale":"The given URL is a web address, not a persistent identifier from a recognized PID scheme. 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[majority verdict 'no' (4/5 passes agreed)]","anchors":["RDA-I3-01M — '(meta)data include references to other (meta)data'","RDA-I3-03M — 'metadata includes qualified references to other metadata'","FsF-I3-01M — F-UJI: 'Metadata includes links between the data and its related entities'"],"scored":false,"signal":null}]},"R":{"name":"Reusable","score":25.0,"criteria":[{"key":"r_reuse_license","label":"Reuse licence","kind":"llm","weight":2.0,"fraction":0.0,"verdict":"no","evidence":null,"grounded":false,"rationale":"The only license mentioned (CC BY) applies to the article, not the data.","anchors":["RDA-R1.1-01M — 'Metadata includes information about the licence under which the data can be reu","RDA-R1.1-02M — 'Metadata refers to a standard reuse licence'","RDA-R1.1-03M — 'Metadata refers to a machine-understandable reuse licence'"],"scored":true,"signal":null},{"key":"r_provenance_methods","label":"Provenance of the data","kind":"llm","weight":1.0,"fraction":1.0,"verdict":"yes","evidence":"NovaSeq Illumina 6000","grounded":true,"rationale":"The key resources table lists the sequencing instrument, providing a proper-noun tool name. 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