Single cell transcriptome profiling of the human alcohol-dependent brain.
Eric Brenner, Gayatri R Tiwari, Manav Kapoor, Yunlong Liu, Amy Brock, R Dayne Mayfield
Author Information
- Eric Brenner: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
- Gayatri R Tiwari: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
- Manav Kapoor: Department of Neuroscience, Icahn School of Medicine at Mt. Sinai, New York, NY 10029, USA.
- Yunlong Liu: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
- Amy Brock: Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
- R Dayne Mayfield: Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, USA.
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 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. 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.
Alcoholism
Animals
Astrocytes
Brain
Computational Biology
Ethanol
Gene Expression Profiling
Humans
Microglia
Prefrontal Cortex
Sequence Analysis, RNA
Single-Cell Analysis
Transcriptome
