Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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

View ORCID ProfileLucas T Graybuck, Adriana 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, Shenqin Yao, Marty Mortrud, John Mich, View ORCID ProfileJeff Goldy, Kimberly A Smith, Nick Dee, View ORCID ProfileZizhen Yao, Ali Cetin, View ORCID ProfileBoaz P 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
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lucas T Graybuck
  • For correspondence: lucasg@alleninstitute.org
Adriana Sedeño-Cortés
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: adrianas@alleninstitute.org
Thuc Nghi Nguyen
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Thuc Nghi Nguyen
  • For correspondence: thucn@alleninstitute.org
Miranda Walker
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: mirandaw@alleninstitute.org
Eric Szelenyi
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: ericsz@alleninstitute.org
Garreck Lenz
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: garreckl@alleninstitute.org
La'Akea Sieverts
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: laakeas@alleninstitute.org
Tae Kyung Kim
CuraCloud Corporation
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tae Kyung Kim
  • For correspondence: sean.taekyung@gmail.com
Emma Garren
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: emmag@alleninstitute.org
Brian Kalmbach
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: briank@alleninstitute.org
Shenqin Yao
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: shenqiny@alleninstitute.org
Marty Mortrud
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: martym@alleninstitute.org
John Mich
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: johnmi@alleninstitute.org
Jeff Goldy
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Jeff Goldy
Kimberly A Smith
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kimberlys@alleninstitute.org
Nick Dee
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: nickd@alleninstitute.org
Zizhen Yao
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Zizhen Yao
Ali Cetin
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: alic@alleninstitute.org
Boaz P Levi
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Boaz P Levi
  • For correspondence: boazl@alleninstitute.org
Ed Lein
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ed Lein
  • For correspondence: edl@alleninstitute.org
Jonathan Ting
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jonathant@alleninstitute.org
Hongkui Zeng
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hongkui Zeng
  • For correspondence: hongkuiz@alleninstitute.org
Tanya Daigle
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Tanya Daigle
  • For correspondence: tanyad@alleninstitute.org
Bosiljka Tasic
Allen Institute for Brain Science;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bosiljka Tasic
  • For correspondence: bosiljkat@alleninstitute.org
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

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.

Footnotes

  • This preprint has been updated from original biorXiv submission. The following are major changes: 1. Correction of GM12878 cell culturing and collection methods. GM12878 is a suspension cell line, not adherent. Thanks to Darren Cusanovich for identifying this error. 2. Addition of GM12878 data from Pliner, et al. (2018) to Supp Fig 4 and updates to some calculations. This better shows the high quality of current sci-ATAC-seq methods. Thanks to Jay Shendure and Darren Cusanovich for recommending this addition. 3. Updated analysis of Cusanovich, Hill, et al. (2018) data in Supp Fig 7 by changing the label metadata column selected. Thanks to Andrew Hill for recommending these higher-resolution labels. 4. Proper citation of Cusanovich, Hill et al. (2018), and discussion of the prior work in Drosophila in Cusanovich, Reddington, Garfield et al. (2018). Thanks to Jay Shendure for identifying these omissions. 5. Listing of R packages used for analysis.

Copyright 
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.
Back to top
PreviousNext
Posted January 31, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs
Lucas T Graybuck, Adriana 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 A Smith, Nick Dee, Zizhen Yao, Ali Cetin, Boaz P Levi, Ed Lein, Jonathan Ting, Hongkui Zeng, Tanya Daigle, Bosiljka Tasic
bioRxiv 525014; doi: https://doi.org/10.1101/525014
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs
Lucas T Graybuck, Adriana 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 A Smith, Nick Dee, Zizhen Yao, Ali Cetin, Boaz P Levi, Ed Lein, Jonathan Ting, Hongkui Zeng, Tanya Daigle, Bosiljka Tasic
bioRxiv 525014; doi: https://doi.org/10.1101/525014

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (1524)
  • Biochemistry (2479)
  • Bioengineering (1731)
  • Bioinformatics (9670)
  • Biophysics (3896)
  • Cancer Biology (2968)
  • Cell Biology (4189)
  • Clinical Trials (135)
  • Developmental Biology (2624)
  • Ecology (4098)
  • Epidemiology (2031)
  • Evolutionary Biology (6894)
  • Genetics (5204)
  • Genomics (6496)
  • Immunology (2183)
  • Microbiology (6937)
  • Molecular Biology (2751)
  • Neuroscience (17261)
  • Paleontology (126)
  • Pathology (425)
  • Pharmacology and Toxicology (705)
  • Physiology (1056)
  • Plant Biology (2488)
  • Scientific Communication and Education (643)
  • Synthetic Biology (831)
  • Systems Biology (2687)
  • Zoology (429)