論文 - 詳細
| RRC ID | 88461 |
|---|---|
| 著者 | Clark IC, Gutiérrez-Vázquez C, Wheeler MA, Li Z, Rothhammer V, Linnerbauer M, Sanmarco LM, Guo L, Blain M, Zandee SEJ, Chao CC, Batterman KV, Schwabenland M, Lotfy P, Tejeda-Velarde A, Hewson P, Manganeli Polonio C, Shultis MW, Salem Y, Tjon EC, Fonseca-Castro PH, Borucki DM, Alves de Lima K, Plasencia A, Abate AR, Rosene DL, Hodgetts KJ, Prinz M, Antel JP, Prat A, Quintana FJ. |
| タイトル | Barcoded viral tracing of single-cell interactions in central nervous system inflammation. |
| ジャーナル | Science |
| Abstract |
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. |
| 巻・号 | 372(6540) |
| 公開日 | 2021-4-23 |
| DOI | 10.1126/science.abf1230 |
| PII | 372/6540/eabf1230 |
| PMID | 33888612 |
| PMC | PMC8157482 |
| MeSH | Animals Antigens, CD / metabolism Astrocytes / physiology* Brain / pathology Brain / physiopathology Cell Communication* Central Nervous System / pathology* Central Nervous System / physiopathology Encephalomyelitis, Autoimmune, Experimental / pathology Encephalomyelitis, Autoimmune, Experimental / physiopathology* Ephrin-B3 / metabolism Herpesvirus 1, Suid / genetics Humans Male Mice Mice, Inbred C57BL Microglia / physiology* Mitochondria / metabolism Multiple Sclerosis / pathology Multiple Sclerosis / physiopathology* NF-kappa B / metabolism Nerve Tissue Proteins / metabolism RNA-Seq Reactive Oxygen Species / metabolism Receptor, EphB3 / antagonists & inhibitors Receptor, EphB3 / metabolism Receptors, Cell Surface / metabolism Semaphorins / metabolism Signal Transduction Single-Cell Analysis* T-Lymphocytes / physiology TOR Serine-Threonine Kinases / metabolism |
| IF | 41.846 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 373 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC05737 |