TY - JOUR T1 - Single cell transcriptome profiling of the human alcohol-dependent brain JF - bioRxiv DO - 10.1101/780304 SP - 780304 AU - Eric Brenner AU - Gayatri R. Tiwari AU - Yunlong Liu AU - Amy Brock AU - R. Dayne Mayfield Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/09/24/780304.abstract N2 - Background Alcoholism remains a prevalent health concern throughout the world. Previous studies have identified transcriptomic patterns in the brain associated with alcohol dependence in both humans and animal models. But none of these studies have systematically investigated expression within the unique cell types present in the brain.Results We utilized single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of over 16,000 nuclei isolated from prefrontal cortex of alcoholic and control individuals. Each nucleus was assigned to one of seven major cell types by unsupervised clustering. Cell type enrichment patterns varied greatly among neuroinflammatory-related genes, which are known to play roles in alcohol dependence and neurodegeneration. Differential expression analysis identified cell type-specific genes with altered expression in alcoholics. The largest number of differentially expressed genes (DEGs), including both protein-coding and non-coding, were detected in astrocytes, oligodendrocytes, and microglia.Conclusions To our knowledge, this is the first single cell transcriptome analysis of alcohol-associated gene expression in any species, and the first such analysis in humans for any addictive substance. These findings greatly advance understanding of transcriptomic changes in the brain of alcohol-dependent individuals. ER -