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- Title
Single cell transcriptome profiling of the human alcohol-dependent brain.
- Authors
Brenner, Eric; Tiwari, Gayatri R.; Kapoor, Manav; Yunlong Liu; Brock, Amy; Mayfield, R. Dayne
- Abstract
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. We utilized single nucleus RNA sequencing (snRNA-seq) to examine the transcriptomes of over 16 000 nuclei isolated from the 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 neuroinf lammatory-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. 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 the understanding of transcriptomic changes in the brain of alcohol-dependent individuals.
- Publication
Human Molecular Genetics, 2020, Vol 29, Issue 7, p1144
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddaa038