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Here we use scRNA-seq and\n                    <jats:italic>in vivo<\/jats:italic>\n                    experiments to show that\n                    <jats:italic>sema4ab<\/jats:italic>\n                    , mainly expressed by lesion-reactive microglia, attenuates regenerative neurogenesis by changing the complex lesion environment. After spinal injury, disruption of\n                    <jats:italic>sema4ab<\/jats:italic>\n                    doubles the number of newly generated progenitor cells and neurons but attenuates axon regrowth and recovery of swimming function. Disruption of the\n                    <jats:italic>plxnb1a\/b<\/jats:italic>\n                    receptors, selectively expressed by neural progenitor cells, increases regenerative neurogenesis. In addition, disruption of\n                    <jats:italic>sema4ab<\/jats:italic>\n                    alters activation state and cytokine expression of microglia, such that fibroblasts increase expression of the cytokine\n                    <jats:italic>tgfb3<\/jats:italic>\n                    , which strongly promotes regenerative neurogenesis. Hence, we propose that\n                    <jats:italic>sema4ab<\/jats:italic>\n                    expression in microglia attenuates regenerative neurogenesis in multiple ways, likely directly through\n                    <jats:italic>plxnb1a\/b<\/jats:italic>\n                    receptors and indirectly, by controlling the inflammatory milieu and\n                    <jats:italic>tgfb3<\/jats:italic>\n                    levels\n                    <jats:italic>.<\/jats:italic>\n                    Targeting Sema4A-dependent signaling in non-regenerating vertebrates may be a future strategy to improve regenerative outcomes.\n                  <\/jats:p>","DOI":"10.1371\/journal.pbio.3003865","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T17:42:19Z","timestamp":1781804539000},"page":"e3003865","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The 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