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National Institute of Environmental Health Sciences

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Publication Detail

Title: Barcoded viral tracing of single-cell interactions in central nervous system inflammation.

Authors: 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

Published In Science, (2021 04 23)

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.

PubMed ID: 33888612 Exiting the NIEHS site

MeSH Terms: 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

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