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

Autor(es):Mostrar menos -

Clark, Iain C. ^{[1, 2]} ; Gutierrez-Vazquez, Cristina ^[1] ; Wheeler, Michael A. ^{[3, 1]} ; Li, Zhaorong ^{[3, 1]} ; Rothhammer, Veit ^{[1, 4]} ; Linnerbauer, Mathias ^{[1, 4]} ; Sanmarco, Liliana M. ^[1] ; Guo, Lydia ^[1] ; Blain, Manon ^[5] ; Zandee, Stephanie E. J. ^[6] ; Chao, Chun-Cheih ^[1] ; Batterman, V, Katelyn ; Schwabenland, Marius ^[7] ; Lotfy, Peter ^{[3, 1]} ; Tejeda-Velarde, Amalia ^{[8, 1, 9]} ; Hewson, Patrick ^[1] ; Polonio, Carolina Manganeli ^[1] ; Shultis, Michael W. ^[1] ; Salem, Yasmin ^[1] ; Tjon, Emily C. ^[1] ; Fonseca-Castro, Pedro H. ^[1] ; Borucki, Davis M. ^[1] ; de Lima, Kalil Alves ^[1] ; Plasencia, Agustin ^[1] ; Abate, Adam R. ^{[10, 11]} ; Rosene, Douglas L. ^[12] ; Hodgetts, Kevin J. ^[1] ; Prinz, Marco ^{[7, 13, 14, 15]} ; Antel, Jack P. ^[5] ; Prat, Alexandre ^[6] ; Quintana, Francisco J. ^{[3, 1]}

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^[1] Harvard Med Sch, Ann Romney Ctr Neurol Dis, Brigham & Womens Hosp, Boston, MA 02115 - USA

^[2] Univ Calif Berkeley, Calif Inst Quantitat Biosci, Dept Bioengn, Berkeley, CA 94720 - USA

^[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 - USA

^[4] Friedrich Alexander Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Neurol, D-91054 Erlangen - Germany

^[5] McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Neuroimmunol Unit, Montreal, PQ H3A 2B4 - Canada

^[6] Univ Montreal CRCHUM, Neuroimmunol Res Lab, Ctr Rech, Ctr Hosp, Montreal, PQ H2X 0A9 - Canada

^[7] Univ Freiburg, Inst Neuropathol, D-79106 Freiburg - Germany

^[8] Inst Ramon y Cajal Invest Sanitaria IRYCIS, Madrid - Spain

^[9] Hosp Univ Ramon y Cajal, Immunol Dept, Madrid - Spain

^[10] Univ Calif San Francisco, Calif Inst Quantitat Biosci, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 - USA

^[11] Chan Zuckerberg Biohub, San Francisco, CA - USA

^[12] Batterman, Katelyn, V, Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 - USA

^[13] Univ Freiburg, Signaling Res Ctr BIOSS, D-79106 Freiburg - Germany

^[14] Univ Freiburg, Signaling Res Ctr CIBSS, D-79106 Freiburg - Germany

^[15] Univ Freiburg, Fac Med, Ctr Basics NeuroModulat NeuroModulBas, D-79106 Freiburg - Germany

• Tipo de documento: Artigo Científico
• Fonte: Science; v. 372, n. 6540, p. 360+, APR 23 2021.
• Citações Web of Science: 1

Resumo

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 microgliaastrocyte 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 microgliaastrocyte interactions and candidate therapeutic targets. (AU)

• Processo FAPESP: 19/13731-0 - MicroRNAs, neurodesenvolvimento e resposta immune antiviral: como eles podem estar conectados?
• Beneficiário: Carolina Manganeli Polonio
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado