Joint single-cell measurements of nuclear proteins and RNA in vivo
Name
nihms-1745895.pdf
Description
Accepted version
Size
4.74 MB
Format
Adobe PDF
Checksum (MD5)
40c59a30b884d96b338c005bdbcc33fe
Author(s)
Chung, Hattie
Parkhurst, Christopher N
Magee, Emma M
Phillips, Devan
Habibi, Ehsan
Chen, Fei
Yeung, Bertrand Z
Waldman, Julia
Artis, David
Regev, Aviv
Date Issued
2021
Journal
Nature Methods
Publisher
Springer Science and Business Media LLC
Citation
Chung, Hattie, Parkhurst, Christopher N, Magee, Emma M, Phillips, Devan, Habibi, Ehsan et al. 2021. "Joint single-cell measurements of nuclear proteins and RNA in vivo." Nature Methods, 18 (10).
Version
Author's final manuscript
Abstract
Identifying gene-regulatory targets of nuclear proteins in tissues is a challenge. Here we describe intranuclear cellular indexing of transcriptomes and epitopes (inCITE-seq), a scalable method that measures multiplexed intranuclear protein levels and the transcriptome in parallel across thousands of nuclei, enabling joint analysis of transcription factor (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 genome-wide associations of each TF and recovered known gene targets. TF-associated genes were coexpressed as distinct modules that each reflected positive or negative TF levels, showing that our approach can disentangle relative putative contributions of TFs to gene expression and add interpretability to inferred 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/S41592-021-01278-1
