Thread by @erik_sci

In my 1st tweetorial, I’m happy to share our preprint—my first, first author manuscript! We used @10xGenomics single-nucleus RNA-seq in a mouse model of electroconvulsive seizures (ECS) to assess activity-regulated gene expression in hippocampal #neurons. biorxiv.org/content/10.110…

Activity-regulated gene expression patterns in the #hippocampus regulate #plasticity, #learning, and #memory, and are linked to risk and treatment response for neuropsychiatric disorders. However, the cell type-specificity of these patterns is still not well characterized.

We sequenced a bunch of neuronal nuclei (15,990) from mouse hippocampus and used graph-based clustering and a priori marker genes to annotate these nuclei across all major hippocampal subregions and neuron types in both of our experimental conditions (Sham and ECS).

Differential expression analysis between conditions revealed ECS-induced upregulation of known activity-regulated genes (Arc, Bdnf) and gene sets associated with synaptic plasticity and growth factor signaling. We also found some new friends, like Mir670hg, a #microRNA host gene!

We looked at differential expression by cell type and found that differences between conditions were mostly driven by granule cells (including genes like Tll1, Baz1a, Inhba), but also noted heterogeneous expression changes in other neuron types, albeit less pronounced than GCs.

With gene set enrichment analysis, we identified biological processes enriched in ECS across cell types, highlighting pathways associated with #synapse function, growth factor signaling, immune regulation, and different post-translational modifications #ubiquitin #phosphorylation

CoGAPS non-negative matrix factorization helped us find gene expression patterns differentially correlated with cell type & ECS, including signatures associated w/ ECS-activated granule and pyramidal neurons. Thanks to @GenesOfEve and @FertigLab for building a great tool for #NMF

Finally, we’ve made our dataset accessible online via an interactive #shiny web app using the #iSEE #Bioconductor package! Thanks to @HeenaDivecha @lcolladotor for building this for us! libd.shinyapps.io/2022_HPC_ARG/

These data pave the way to a more complete understanding of activity-regulated gene expression in hippocampus. Our work may also help inform and improve translational studies of psychiatric treatments involving activity-regulated genes, such as electroconvulsive therapy (#ECT).

Thanks to all involved with this study: mentors @martinowk, @stephaniehicks, & @kr_maynard along with co-authors @KyndallNicholas @mattntran @HeenaDivecha @lcolladotor! Also, thanks to @LieberInstitute @CMM_JHU @HopkinsMedicine @ChanZuckerberg @NIH @NIMHgov for supporting us!