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

Simultaneous single cell measurements of intranuclear proteins and gene expression

View ORCID ProfileHattie Chung, Christopher N. Parkhurst, Emma M. Magee, View ORCID ProfileDevan Phillips, View ORCID ProfileEhsan Habibi, Fei Chen, View ORCID ProfileBertrand Yeung, View ORCID ProfileJulia Waldman, View ORCID ProfileDavid Artis, Aviv Regev
doi: https://doi.org/10.1101/2021.01.18.427139
Hattie Chung
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hattie Chung
  • For correspondence: hchung@broadinstitute.org aregev@broadinstitute.org
Christopher N. Parkhurst
2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emma M. Magee
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Devan Phillips
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Devan Phillips
Ehsan Habibi
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ehsan Habibi
Fei Chen
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bertrand Yeung
3BioLegend Inc, San Diego, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bertrand Yeung
Julia Waldman
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Julia Waldman
David Artis
2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY, USA
4Friedman Center for Nutrition and Inflammation, Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David Artis
Aviv Regev
1Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA, USA
5Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
6Genentech, 1 DNA Way, South San Francisco, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: hchung@broadinstitute.org aregev@broadinstitute.org
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Identifying gene regulatory targets of nuclear proteins in tissues remains a challenge. Here we describe intranuclear Cellular Indexing of Transcriptomes and Epitopes (inCITE-seq), a scalable method for measuring multiplexed intranuclear protein levels and the transcriptome in parallel in thousands of cells, enabling joint analysis of TF levels and gene expression in vivo. We apply inCITE-seq to characterize cell state-related changes upon pharmacological induction of neuronal activity in the mouse brain. Modeling gene expression as a linear combination of quantitative protein levels revealed the genome-wide effect of each TF and recovered known targets. Cell type-specific genes associated with each TF were co-expressed as distinct modules that each corresponded to positive or negative TF levels, showing that our approach can disentangle relative contributions of TFs to gene expression and add interpretability to gene networks. InCITE-seq can illuminate how combinations of nuclear proteins shape gene expression in native tissue contexts, with direct applications to solid or frozen tissues and clinical specimens.

Competing Interest Statement

A.R. is a founder and equity holder of Celsius Therapeutics, an equity holder in Immunitas Therapeutics, and until August 31, 2020 was an SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and ThermoFisher Scientific. From August 1, 2020, A.R. is an employee of Genentech.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted January 19, 2021.
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.
Simultaneous single cell measurements of intranuclear proteins and gene expression
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Simultaneous single cell measurements of intranuclear proteins and gene expression
Hattie Chung, Christopher N. Parkhurst, Emma M. Magee, Devan Phillips, Ehsan Habibi, Fei Chen, Bertrand Yeung, Julia Waldman, David Artis, Aviv Regev
bioRxiv 2021.01.18.427139; doi: https://doi.org/10.1101/2021.01.18.427139
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Simultaneous single cell measurements of intranuclear proteins and gene expression
Hattie Chung, Christopher N. Parkhurst, Emma M. Magee, Devan Phillips, Ehsan Habibi, Fei Chen, Bertrand Yeung, Julia Waldman, David Artis, Aviv Regev
bioRxiv 2021.01.18.427139; doi: https://doi.org/10.1101/2021.01.18.427139

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

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4658)
  • Biochemistry (10313)
  • Bioengineering (7636)
  • Bioinformatics (26241)
  • Biophysics (13481)
  • Cancer Biology (10650)
  • Cell Biology (15361)
  • Clinical Trials (138)
  • Developmental Biology (8464)
  • Ecology (12776)
  • Epidemiology (2067)
  • Evolutionary Biology (16794)
  • Genetics (11373)
  • Genomics (15431)
  • Immunology (10580)
  • Microbiology (25087)
  • Molecular Biology (10172)
  • Neuroscience (54233)
  • Paleontology (398)
  • Pathology (1660)
  • Pharmacology and Toxicology (2884)
  • Physiology (4326)
  • Plant Biology (9213)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2545)
  • Systems Biology (6761)
  • Zoology (1459)