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

Benjamin Lacar, Sara B. Linker, Baptiste N. Jaeger, Suguna Rani Krishnaswami, Jerika J. Barron, Martijn J. E. Kelder, Sarah L. Parylak, Apuã C. M. Paquola, Pratap Venepally, Mark Novotny, Carolyn O'Connor, Conor Fitzpatrick, Jennifer A. Erwin, Jonathan Y. Hsu, David Husband, Michael J. McConnell, Roger Lasken and Fred H. Gage ()
Additional contact information
Benjamin Lacar: Laboratory of Genetics, The Salk Institute for Biological Studies
Sara B. Linker: Laboratory of Genetics, The Salk Institute for Biological Studies
Baptiste N. Jaeger: Laboratory of Genetics, The Salk Institute for Biological Studies
Suguna Rani Krishnaswami: J. Craig Venter Institute
Jerika J. Barron: Laboratory of Genetics, The Salk Institute for Biological Studies
Martijn J. E. Kelder: Laboratory of Genetics, The Salk Institute for Biological Studies
Sarah L. Parylak: Laboratory of Genetics, The Salk Institute for Biological Studies
Apuã C. M. Paquola: Laboratory of Genetics, The Salk Institute for Biological Studies
Pratap Venepally: J. Craig Venter Institute
Mark Novotny: Laboratory of Genetics, The Salk Institute for Biological Studies
Carolyn O'Connor: Laboratory of Genetics, The Salk Institute for Biological Studies
Conor Fitzpatrick: Laboratory of Genetics, The Salk Institute for Biological Studies
Jennifer A. Erwin: Laboratory of Genetics, The Salk Institute for Biological Studies
Jonathan Y. Hsu: Laboratory of Genetics, The Salk Institute for Biological Studies
David Husband: Laboratory of Genetics, The Salk Institute for Biological Studies
Michael J. McConnell: University of Virginia School of Medicine
Roger Lasken: J. Craig Venter Institute
Fred H. Gage: Laboratory of Genetics, The Salk Institute for Biological Studies

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11022

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