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It is becoming increasingly recognized that ependymal cells assume a reactive state in response to aging and disease, including conditions involving hypoxia, hydrocephalus, neurodegeneration, and neuroinflammation. Yet what transcriptional signatures govern these reactive states and whether this reactivity shares any similarities with classical descriptions of glial reactivity (i.e., in astrocytes) remain largely unexplored. Using single\u2010cell transcriptomics, we interrogated this phenomenon by directly comparing the reactive ependymal cell transcriptome to the reactive astrocyte transcriptome using a well\u2010established model of autoimmune\u2010mediated neuroinflammation (MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    EAE). In doing so, we unveiled\n                    <jats:italic>core glial reactivity\u2010associated genes<\/jats:italic>\n                    that defined the reactive ependymal cell and astrocyte response to MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    EAE. Interestingly, known reactive astrocyte genes from other CNS injury\/disease contexts were also up\u2010regulated by MOG\n                    <jats:sub>35\u201055<\/jats:sub>\n                    EAE ependymal cells, suggesting that this state may be conserved in response to a variety of pathologies. We were also able to recapitulate features of the reactive ependymal cell state acutely using a classic neuroinflammatory cocktail (IFN\u03b3\/LPS) both in\u00a0vitro and in\u00a0vivo. Taken together, by comparing reactive ependymal cells and astrocytes, we identified a conserved signature underlying glial reactivity that was present in several neuroinflammatory contexts. Future work will explore the mechanisms driving ependymal reactivity and assess downstream functional consequences.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16120-fig-0005-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16120","type":"journal-article","created":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T04:09:16Z","timestamp":1714795756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ependymal cells undergo astrocyte\u2010like reactivity in response to neuroinflammation"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-0973","authenticated-orcid":false,"given":"Adam M. 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