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Clark, Iain C; Gutiérrez-Vázquez, Cristina; Wheeler, Michael A; Li, Zhaorong; Rothhammer, Veit; Linnerbauer, Mathias; Sanmarco, Liliana M; Guo, Lydia; Blain, Manon; Zandee, Stephanie E J; Chao, Chun-Cheih; Batterman, Katelyn V; Schwabenland, Marius; Lotfy, Peter; Tejeda-Velarde, Amalia; Hewson, Patrick; Manganeli Polonio, Carolina; Shultis, Michael W; Salem, Yasmin; Tjon, Emily C; Fonseca-Castro, Pedro H; Borucki, Davis M; Alves de Lima, Kalil; Plasencia, Agustin; Abate, Adam R; Rosene, Douglas L; Hodgetts, Kevin J; Prinz, Marco; Antel, Jack P; Prat, Alexandre; Quintana, Francisco J
Science (American Association for the Advancement of Science), 04/2021, Letnik: 372, Številka: 6540Journal Article
Cell-cell interactions control the physiology and pathology of the central nervous system (CNS). To study astrocyte cell interactions in vivo, we developed rabies barcode interaction detection followed by sequencing (RABID-seq), which combines barcoded viral tracing and single-cell RNA sequencing (scRNA-seq). Using RABID-seq, we identified axon guidance molecules as candidate mediators of microglia-astrocyte interactions that promote CNS pathology in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis (MS). In vivo cell-specific genetic perturbation EAE studies, in vitro systems, and the analysis of MS scRNA-seq datasets and CNS tissue established that Sema4D and Ephrin-B3 expressed in microglia control astrocyte responses via PlexinB2 and EphB3, respectively. Furthermore, a CNS-penetrant EphB3 inhibitor suppressed astrocyte and microglia proinflammatory responses and ameliorated EAE. In summary, RABID-seq identified microglia-astrocyte interactions and candidate therapeutic targets.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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