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 re-capitulates 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 pseudo-temporal 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. SOURCE: Fred,H,Gage (gage@salk.edu) -  The Salk Institute for Biological Studies

Pluto Bioinformatics

GSE77067: RNA-sequencing of single whole cells and nuclei from mouse dentate granule cells