Application of Single Cell Transcriptome Sequencing in Drug Addiction Research

Drug addiction is a complicated central nervous system (CNS) disorder. Both basic and clinical studies have confirmed that the neural mechanisms of drug addiction are progressively altered at different stages of the development of addictive behaviors. Genomic studies using technologies such as whole-genome association studies, whole-genome sequencing, whole-exome sequencing or high-throughput transcriptome sequencing have provided insight into the genetic vulnerability of mental disorders, including drug addiction. The single nucleotide polymorphism detection techniques or sequencing technologies mainly predict genetic risk loci for diseases. However, the occurrence of many CNS disorders is closely related to environmental factors and there is brain region-specific cellular heterogeneity information on the expression of relevant genes at different stages of disease development. Therefore, traditional molecular genetic studies have limitations in explaining the pathogenesis of CNS disorder. Single-cell RNA sequencing (ScRNA-seq) technologies, which target individual cells for transcript level determination, avoid the disadvantages of traditional sequencing for detecting the average transcript level of cell populations and can quantitatively describe cellular heterogeneity. In recent years, single-cell transcriptional sequencing technology has been applied to the study of drug addiction. The cortico-mesolimbic system, corticostriatal-thalamo-cortical pathway and the hippocampus are important brain regions associated with drug addiction. It was found that more neuronal subtypes exist in both the striatum and hippocampus than previously known. In the cortex, pyramidal neurons exhibit a projection-specific gene expression profile. In rodent models experiencing from cocaine, morphine, and tetrahydrocannabinol, recent studies have identified single-cell transcriptome alterations in the nucleus accumbens and prefrontal cortex, the key brain regions for rewarding. These studies have advanced the mechanisms of drug addiction and drug development to the level of cellular resolution in specific brain regions. This review summarizes the important applications of single-cell RNA-Seq in neuroscience research and uses drug addiction as an example to illustrate its value in the study of CNS disorders.