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To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of na\u00efve 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\u2013nerve 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\n                    <jats:italic>\n                      Sarm1\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice, in which Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in\n                    <jats:italic>\n                      Sarm1\n                      <jats:sup>-\/-<\/jats:sup>\n                    <\/jats:italic>\n                    mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the na\u00efve and injured PNS and report on hundreds of ligand\u2013receptor 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):\n                    <jats:ext-link ext-link-type=\"uri\" xlink:href=\"https:\/\/cdb-rshiny.med.umich.edu\/Giger_iSNAT\/\">https:\/\/cdb-rshiny.med.umich.edu\/Giger_iSNAT\/<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.7554\/elife.80881","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T08:00:19Z","timestamp":1671004819000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80881","source":"Crossref","is-referenced-by-count":101,"title":["The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7574-7163","authenticated-orcid":true,"given":"Xiao-Feng","family":"Zhao","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell and Developmental Biology, University of Michigan-Ann Arbor","place":["Ann Arbor, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7779-086X","authenticated-orcid":true,"given":"Lucas D","family":"Huffman","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Cell and Developmental Biology, University of Michigan-Ann Arbor","place":["Ann Arbor, United States"]},{"id":[{"id":"https:\/\/ror.org\/00jmfr291","id-type":"ROR","asserted-by":"publisher"}],"name":"Neuroscience Graduate Program, University of Michigan\u2013Ann 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