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Barcoded viral tracing of single-cell interactions in central nervous system inflammation.
- Source :
-
Science (New York, N.Y.) [Science] 2021 Apr 23; Vol. 372 (6540). - Publication Year :
- 2021
-
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.<br /> (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Subjects :
- Animals
Antigens, CD metabolism
Brain pathology
Brain physiopathology
Central Nervous System physiopathology
Encephalomyelitis, Autoimmune, Experimental pathology
Ephrin-B3 metabolism
Herpesvirus 1, Suid genetics
Humans
Male
Mice
Mice, Inbred C57BL
Mitochondria metabolism
Multiple Sclerosis pathology
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
T-Lymphocytes physiology
TOR Serine-Threonine Kinases metabolism
Astrocytes physiology
Cell Communication
Central Nervous System pathology
Encephalomyelitis, Autoimmune, Experimental physiopathology
Microglia physiology
Multiple Sclerosis physiopathology
Single-Cell Analysis
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 372
- Issue :
- 6540
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 33888612
- Full Text :
- https://doi.org/10.1126/science.abf1230