Single-nucleus transcriptome analysis reveals cell-type-specific molecular signatures across reward circuitry in the human brain

Neuron. 2021 Oct 6;109(19):3088-3103.e5. doi: 10.1016/j.neuron.2021.09.001. Epub 2021 Sep 27.

Abstract

Single-cell gene expression technologies are powerful tools to study cell types in the human brain, but efforts have largely focused on cortical brain regions. We therefore created a single-nucleus RNA-sequencing resource of 70,615 high-quality nuclei to generate a molecular taxonomy of cell types across five human brain regions that serve as key nodes of the human brain reward circuitry: nucleus accumbens, amygdala, subgenual anterior cingulate cortex, hippocampus, and dorsolateral prefrontal cortex. We first identified novel subpopulations of interneurons and medium spiny neurons (MSNs) in the nucleus accumbens and further characterized robust GABAergic inhibitory cell populations in the amygdala. Joint analyses across the 107 reported cell classes revealed cell-type substructure and unique patterns of transcriptomic dynamics. We identified discrete subpopulations of D1- and D2-expressing MSNs in the nucleus accumbens to which we mapped cell-type-specific enrichment for genetic risk associated with both psychiatric disease and addiction.

Keywords: addiction; brain; genomics; neuroscience; psychiatry; reward; single-cell; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / physiology*
  • Brain Mapping
  • Cell Nucleus / genetics*
  • Cell Nucleus / physiology*
  • Gene Expression Profiling*
  • Genome-Wide Association Study
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Interneurons / physiology
  • Mental Disorders / genetics
  • Nerve Net / physiology*
  • Neurons / physiology
  • Reward*
  • Sequence Analysis, RNA
  • Substance-Related Disorders / genetics
  • gamma-Aminobutyric Acid / physiology

Substances

  • gamma-Aminobutyric Acid