Combining long-term circuit mapping and network transcriptomics with SiR-N2c

Lee, Hassal, Ciabatti, Ernesto, González-Rueda, Ana, Williams, Elena, Nugent, Fiona, Mookerjee, Souradip, Morgese, Fabio, Tripodi, Marco (March 2023) Combining long-term circuit mapping and network transcriptomics with SiR-N2c. Nature Methods. ISSN 1548-7091 (Public Dataset)

DOI: 10.1038/s41592-023-01787-1


An exciting frontier in circuit neuroscience lies at the intersection between neural network mapping and single-cell genomics. Monosynaptic rabies viruses provide a promising platform for the merger of circuit mapping methods with -omics approaches. However, three key limitations have hindered the extraction of physiologically meaningful gene expression profiles from rabies-mapped circuits: inherent viral cytotoxicity, high viral immunogenicity and virus-induced alteration of cellular transcriptional regulation. These factors alter the transcriptional and translational profiles of infected neurons and their neighboring cells. To overcome these limitations we applied a self-inactivating genomic modification to the less immunogenic rabies strain, CVS-N2c, to generate a self-inactivating CVS-N2c rabies virus (SiR-N2c). SiR-N2c not only eliminates undesired cytotoxic effects but also substantially reduces gene expression alterations in infected neurons and dampens the recruitment of innate and acquired immune responses, thus enabling open-ended interventions on neural networks and their genetic characterization using single-cell genomic approaches.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
Investigative techniques and equipment
organs, tissues, organelles, cell types and functions > tissues types and functions > neural networks
organism description > virus > rabies virus
Investigative techniques and equipment > assays > Single cell sequencing
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
organism description > virus
CSHL Authors:
Communities: CSHL labs > Janowitz lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 2 March 2023
Date Deposited: 08 Mar 2023 15:40
Last Modified: 10 Jan 2024 20:13
PMCID: PMC7614628
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