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Nat Commun. 2016 Apr 19;7:11022. doi: 10.1038/ncomms11022.

Nuclear RNA-seq of single neurons reveals molecular signatures of activation.

Author information

1
Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 N Torrey Pines Road, La Jolla, California 92037-1002, USA.
2
J. Craig Venter Institute, La Jolla, California 92037, USA.
3
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.

Abstract

Single-cell sequencing methods have emerged as powerful tools for identification of heterogeneous cell types within defined brain regions. Application of single-cell techniques to study the transcriptome of activated neurons can offer insight into molecular dynamics associated with differential neuronal responses to a given experience. Through evaluation of common whole-cell and single-nuclei RNA-sequencing (snRNA-seq) methods, here we show that snRNA-seq faithfully recapitulates transcriptional patterns associated with experience-driven induction of activity, including immediate early genes (IEGs) such as Fos, Arc and Egr1. SnRNA-seq of mouse dentate granule cells reveals large-scale changes in the activated neuronal transcriptome after brief novel environment exposure, including induction of MAPK pathway genes. In addition, we observe a continuum of activation states, revealing a pseudotemporal pattern of activation from gene expression alone. In summary, snRNA-seq of activated neurons enables the examination of gene expression beyond IEGs, allowing for novel insights into neuronal activation patterns in vivo.

PMID:
27090946
PMCID:
PMC4838832
DOI:
10.1038/ncomms11022
[Indexed for MEDLINE]
Free PMC Article

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