{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:20:56Z","timestamp":1787782856287,"version":"build-2784847793"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The secondary injury cascade following spinal cord injury (SCI) involves substantial metabolic reprogramming and immune responses. However, whether transcriptional signatures related to lactylation, ferroptosis, and neuroinflammation show coordinated changes after SCI, and which cellular states are associated with these signatures, remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Public bulk transcriptomic datasets (GSE47681 and GSE5296) and a single-cell RNA-seq dataset (GSE162610) were integrated. Bioinformatic analyses included single-sample gene set enrichment analysis (ssGSEA), weighted gene co-expression network analysis (WGCNA), protein-protein interaction analysis, pseudotime trajectory inference, and\n                      <jats:italic>in silico<\/jats:italic>\n                      perturbation analysis. A C5 unilateral contusion SCI mouse model was used for transcriptomic validation, behavioral assessments, Western blotting, and immunofluorescence. Human peripheral blood RNA-seq data (GSE151371) were used as an exploratory external reference for systemic SCI-associated expression patterns.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bulk transcriptomic analysis revealed coordinated elevation of lactylation-related, ferroptosis-related, and inflammation-related signature scores after SCI, with the highest scores observed at 3 days post-injury. Single-cell RNA-seq localized these signatures predominantly to expanded disease-associated microglia (DAM)-like states. Network screening prioritized vimentin (Vim) as a candidate hub gene associated with the three signatures, and Vim-high pathological microglia exhibited an activated inflammatory-metabolic transcriptional state. In the SCI mouse model, VIM, pan-lysine lactylation (pan-Kla), acyl-CoA synthetase long-chain family member 4 (ACSL4), and interleukin-1\u03b2 (IL-1\u03b2) were upregulated in whole-lesion spinal cord tissue. Immunofluorescence further showed increased VIM, pan-Kla, and ACSL4 signals with spatial overlap within IBA1-positive cells after SCI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Pathological DAM-like microglia represent major microglial states exhibiting concurrent lactylation-related, ferroptosis-related, and inflammatory signatures after SCI. VIM was prioritized as a candidate hub associated with this pathological microglial program. These findings provide a cellular and molecular framework for future mechanistic studies of secondary SCI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1902559","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:10:23Z","timestamp":1787782223000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics identifies a VIM-associated microglial program linked to lactylation, ferroptosis, and neuroinflammation after spinal cord injury"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiayu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Spinal Surgery, The First People\u2019s Hospital of Chenzhou","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, The Second Affiliated Hospital and Yuying Children\u2019s Hospital of Wenzhou Medical University, The Second School of Clinical Medicine, Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zucheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Spine Surgery, Department of Orthopaedics, Nanfang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Spinal Surgery, The First People\u2019s Hospital of Chenzhou","place":["Chenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17018","DOI":"10.1038\/nrdp.2017.18","article-title":"Traumatic spinal cord injury","volume":"3","author":"Ahuja","year":"2017","journal-title":"Nat. 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