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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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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]
Total Authors: 31
Affiliation:
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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
Total Affiliations: 15
Document type: Journal article
Source: Science; v. 372, n. 6540, p. 360+, APR 23 2021.
Web of Science Citations: 1
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 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)

FAPESP's process: 19/13731-0 - MicroRNAs, neurodevelopment and antiviral immune response: how they can be connected?
Grantee:Carolina Manganeli Polonio
Support Opportunities: Scholarships abroad - Research Internship - Doctorate