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

被引：276

作者：

Lacar, Benjamin ^{[1
]}

Linker, Sara B. ^{[1
]}

Jaeger, Baptiste N. ^{[1
]}

Krishnaswami, Suguna ^{[2
]}

Barron, Jerika ^{[1
]}

Kelder, Martijn ^{[1
]}

Parylak, Sarah ^{[1
]}

Paquola, Apua ^{[1
]}

Venepally, Pratap ^{[2
]}

Novotny, Mark ^{[1
]}

O'Connor, Carolyn ^{[1
]}

Fitzpatrick, Conor ^{[1
]}

Erwin, Jennifer ^{[1
]}

Hsu, Jonathan Y. ^{[1
]}

Husband, David ^{[1
]}

McConnell, Michael J. ^{[3
]}

Lasken, Roger ^{[2
]}

Gage, Fred H. ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA

[2] J Craig Venter Inst, La Jolla, CA 92037 USA

[3] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

关键词：

C-FOS; GENE-EXPRESSION; DENTATE GYRUS; MEMBRANE DEPOLARIZATION; DOUBLE DISSOCIATION; NERVOUS-SYSTEM; CELL; CALCIUM; PROTEIN; TRANSCRIPTOME;

D O I：

10.1038/ncomms11022

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 68 条

[31] Functional identification of an aggression locus in the mouse hypothalamus [J].