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Using RNA sequencing, we identified protein arginine methyltransferase 6 (PRMT6) as a key regulator of this disparity, upregulated in activated microglia at adult SCI lesions but maintained at low levels in neonatal microglia after injury. In adult mice,\n                    <jats:italic>Prmt6<\/jats:italic>\n                    deficiency restored microglial homeostasis, evidenced by increased P2Y12\/TMEM119 and reduced CD68, while reducing scar formation and enhancing axonal regrowth and motor recovery. Microglia\u2010specific\n                    <jats:italic>Prmt6<\/jats:italic>\n                    knockdown or PRMT6 inhibitor administration recapitulated these effects. Mechanistically, PRMT6 deposits H3R2me2a at the\n                    <jats:italic>Ppargc1a<\/jats:italic>\n                    promoter to repress peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator\u20101\u03b1\uff08PGC\u20101\u03b1\uff09, thereby inhibiting fatty acid oxidation (FAO) and disrupting microglial homeostasis. Loss of\n                    <jats:italic>Prmt6<\/jats:italic>\n                    alleviates this epigenetic repression, restoring FAO and microglial homeostasis. These findings establish PRMT6 as a novel epigenetic regulator linking microglial dyshomeostasis and metabolic dysfunction to maladaptive scar formation in adult SCI, highlighting PRMT6 inhibition as a promising therapeutic strategy to reprogram microglial metabolism and promote neural repair.\n                  <\/jats:p>","DOI":"10.1002\/advs.75325","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T11:33:57Z","timestamp":1776425637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prmt6 Deficiency or Inhibition Restores Microglial Homeostasis and Promotes Scar\u2010Limited Repair in Adult Spinal Cord Injury"],"prefix":"10.1002","volume":"13","author":[{"given":"Weilin","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Orthopaedics Changzheng Hospital Naval Medical University  Shanghai 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