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

Authors :
Jonathan Y. Hsu
Pratap Venepally
Carolyn O’Connor
Benjamin Lacar
Roger S. Lasken
Jerika J. Barron
Baptiste N. Jaeger
Suguna Rani Krishnaswami
Sara B. Linker
Fred H. Gage
Martijn J. E. Kelder
David Husband
Jennifer A. Erwin
Michael J. McConnell
Conor Fitzpatrick
Apuã C. M. Paquola
Sarah L. Parylak
Mark Novotny
Source :
Nature Communications, Vol 7, Iss 1, Pp 1-13 (2016)
Publication Year :
2016
Publisher :
Nature Portfolio, 2016.

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.

Details

Language :
English
ISSN :
20411723
Volume :
7
Issue :
1
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi.dedup.....5e95ae39c0d5ec1ab24160adf8c5b520