Cell-type specific transcriptomics of the the dlPFC in females with MDD [single-nucleus RNA-seq]

We performed high-throughput snRNA-seq using the 10X Genomics Chromium platform on archived post-mortem dorsolateral prefrontal cortex (BA9) tissue in female MDD subjects who died by suicide and in female control subjects to identify cell-type specific differentially expressed genes. We further re-processed in parallel a previously generated snRNA-seq dataset in males with or without MDD to generate comparable differential expression results and compare the cell-type specific MDD-associated differences between the sexes. Overall design: 10X Genomics Chromium snRNA-seq was performed on nuclei extracted from BA9 of the post-mortem brain tissue of 18 control subjects and 20 MDD cases who died by suicide. All subjects were female. We performed unsupervised clustering and pseudobulk differential gene expression was performed between cases and controls for each cluster and each broad brain cell type. The library preparation was performed with the Chromium Single Cell 3' Reagent Kits v3.1 or v2. Paired-end sequencing was performed on the Illumina NovaSeq 6000 or with BGI DNBSeq. FASTQ files were produced with Cellranger v3.1.0 mkfastq. Alignments and gene counts were generated with Cellranger v5.1.0 count. Additionally, FASTQ files previously produced from a male cohort (GSE144136) were realigned and recounted, and raw count data from both sexes, which were input into differential expression analysis, along with the cell type annotations are included in the counts matrix provided.