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Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs

View ORCID ProfileLucas T. Graybuck, Adriana E. Sedeño-Cortés, View ORCID ProfileThuc Nghi Nguyen, Miranda Walker, Eric Szelenyi, Garreck Lenz, La’Akea Sieverts, View ORCID ProfileTae Kyung Kim, Emma Garren, Brian Kalmbach, View ORCID ProfileShenqin Yao, Marty Mortrud, John Mich, View ORCID ProfileJeff Goldy, Kimberly Smith, Nick Dee, Zizhen Yao, Ali Cetin, View ORCID ProfileBoaz Levi, View ORCID ProfileEd Lein, Jonathan Ting, View ORCID ProfileHongkui Zeng, View ORCID ProfileTanya Daigle, View ORCID ProfileBosiljka Tasic
doi: https://doi.org/10.1101/525014
Lucas T. Graybuck
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Adriana E. Sedeño-Cortés
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Thuc Nghi Nguyen
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Miranda Walker
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Eric Szelenyi
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Garreck Lenz
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La’Akea Sieverts
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Tae Kyung Kim
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Emma Garren
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Brian Kalmbach
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Shenqin Yao
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Marty Mortrud
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John Mich
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Jeff Goldy
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Kimberly Smith
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Nick Dee
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Zizhen Yao
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Ali Cetin
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Boaz Levi
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Ed Lein
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Jonathan Ting
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Hongkui Zeng
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Tanya Daigle
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Bosiljka Tasic
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Abstract

Labeling and perturbation of specific cell types in multicellular systems has transformed our ability to understand them. The rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient access to these newly discovered types. To enable access to specific neural populations in the mouse cortex, we have collected single cell chromatin accessibility data from select cell types. We clustered the single cell data and mapped them to single cell transcriptomics to identify highly specific enhancers for cell subclasses. These enhancers, when cloned into AAVs and delivered to the brain by retro orbital injections, transgene expression in specific cell subclasses throughout the mouse brain. This approach will enable functional investigation of cell types in the mouse cortex and beyond.

One sentence Summary Combining scATAC-seq and scRNA-seq identifies subclass-specific enhancers to label cells in mouse cortex at high resolution

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted January 31, 2019.
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Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs
Lucas T. Graybuck, Adriana E. Sedeño-Cortés, Thuc Nghi Nguyen, Miranda Walker, Eric Szelenyi, Garreck Lenz, La’Akea Sieverts, Tae Kyung Kim, Emma Garren, Brian Kalmbach, Shenqin Yao, Marty Mortrud, John Mich, Jeff Goldy, Kimberly Smith, Nick Dee, Zizhen Yao, Ali Cetin, Boaz Levi, Ed Lein, Jonathan Ting, Hongkui Zeng, Tanya Daigle, Bosiljka Tasic
bioRxiv 525014; doi: https://doi.org/10.1101/525014
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Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs
Lucas T. Graybuck, Adriana E. Sedeño-Cortés, Thuc Nghi Nguyen, Miranda Walker, Eric Szelenyi, Garreck Lenz, La’Akea Sieverts, Tae Kyung Kim, Emma Garren, Brian Kalmbach, Shenqin Yao, Marty Mortrud, John Mich, Jeff Goldy, Kimberly Smith, Nick Dee, Zizhen Yao, Ali Cetin, Boaz Levi, Ed Lein, Jonathan Ting, Hongkui Zeng, Tanya Daigle, Bosiljka Tasic
bioRxiv 525014; doi: https://doi.org/10.1101/525014

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