| First Author | Clark IC | Year | 2021 |
| Journal | Science | Volume | 372 |
| Issue | 6540 | PubMed ID | 33888612 |
| Mgi Jnum | J:363907 | Mgi Id | MGI:8164435 |
| Doi | 10.1126/science.abf1230 | Citation | Clark IC, et al. (2021) Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science 372(6540) |
| abstractText | 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. |
