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

Clark IC, Gutiérrez-Vázquez C, Wheeler MA, Li Z, Rothhammer V, Linnerbauer M, Sanmarco LM, Guo L, Blain M, Zandee SE, Chao CC, Batterman KV, Schwabenland M, Lotfy P, Tejeda-Velarde A, Hewson P, Polonio CM, Shultis MW, Salem Y, Tjon EC, Fonseca-Castro PH, Borucki DM, de Lima KA, Plasencia A, Abate AR, Rosene DL, Hodgetts KJ, Prinz M, Antel JP, Prat A, Quintana FJ (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Science American Association for the Advancement of Science

Book Volume: 372

Article Number: eabf1230

Journal Issue: 6540

DOI: 10.1126/science.abf1230

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.

Authors with CRIS profile

Veit Rothhammer Heisenbergprofessur für Neuroimmunologie Mathias Linnerbauer Department of Neurology

Involved external institutions

Veterans Affairs Healthcare System Boston and Harvard Medical School US United States (USA) (US) Montreal Neurological Institute and Hospital (MNI, The Neuro) CA Canada (CA) Centre hospitalier de l'Université de Montréal (CHUM) CA Canada (CA) Boston Medical Center (BMC) US United States (USA) (US) Albert-Ludwigs-Universität Freiburg DE Germany (DE) University of California San Francisco (UCSF) US United States (USA) (US)

How to cite

APA:

Clark, I.C., Gutiérrez-Vázquez, C., Wheeler, M.A., Li, Z., Rothhammer, V., Linnerbauer, M.,... Quintana, F.J. (2021). Barcoded viral tracing of single-cell interactions in central nervous system inflammation. Science, 372(6540). https://doi.org/10.1126/science.abf1230

MLA:

Clark, Iain C., et al. "Barcoded viral tracing of single-cell interactions in central nervous system inflammation." Science 372.6540 (2021).

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