Integrative multi-omics landscape of fluoxetine action across 27 brain regions (single cell profiling for 2 regions)

We constructed a comprehensive multi-omics map of the molecular effects of fluoxetine (an SSRI antidepressant) in 27 rat brain regions. We profiled gene expression (bulk RNA-seq, 210 datasets) and chromatin state (bulk chromatin immunoprecipitation sequencing (ChIP-seq) for the histone marker H3K27ac, 100 datasets) in a broad, unbiased panel of 27 brain regions across the entire rodent brain, in naive and fluoxetine-treated animals. We complemented this approach with single-cell RNA-seq (scRNA-seq) analysis of two brain regions (20 datasets). Remarkably, in the single-cell RNA-seq profiling we observed profound changes in the transcripts of hippocampal dorDG and venDG (~500 DEGs in specific cell types). Using diverse integrative data analysis techniques we characterized the complex and multifaceted effects of fluoxetine on region-specific and cell-type-specific gene regulatory networks and pathways. We leveraged this atlas to identify fluoxetine-modulated genes and gene-regulatory loci, predict enriched motifs that suggest potential upstream regulators, and validate global mechanisms of fluoxetine action. To complement our multi-regional epigenome map, we used single cell RNA-seq to profile genome-wide fluoxetine-induced transcriptome changes in 2 hippocampal brain regions. Here we deposit these single cell RNA-seq profiles (2 regions, 2 treatment groups - Sham and Fluoxetine, 5 replicates; 30 MUX libraries, postQC- 3517 cells). To reduce the effects of inter-animal biological variation each RNA-seq sample was pooled from 3 animals (15 in Sham, 15 in FT; 30 animals in total).