An overview of human single-cell RNA sequencing studies in neurobiological disease

Abstract

Neurobiological disorders are highly prevalent medical conditions that contribute to significant morbidity and mortality. Single-cell RNA sequencing (scRNA-seq) is a technique that measures gene expression in individual cells. In this review, we survey scRNA-seq studies of tissues from patients suffering from neurobiological disease. This includes postmortem human brains and organoids derived from peripheral cells. We highlight a range of conditions, including epilepsy, cognitive disorders, substance use disorders, and mood disorders. These findings provide new insights into neurobiological disease in multiple ways, including discovering novel cell types or subtypes involved in disease, proposing new pathophysiological mechanisms, uncovering novel drug targets, or identifying potential biomarkers. We discuss the quality of these findings and suggest potential future directions and areas open for additional research, including studies of non-cortical brain regions and additional conditions such as anxiety disorders, mood disorders, and sleeping disorders. We argue that additional scRNA-seq of tissues from patients suffering from neurobiological disease could advance our understanding and treatment of these conditions.

Keywords: Brain; Human; Neurobiological; Organoids; Postmortem; Single-cell RNA sequencing.

Fig. 1.

A diagram of sc- or snRNA-seq studies in the tissues of people with neurobiological disorders. A.) Brain regions in which sc- or snRNA-seq have been performed are outlined and the neurobiological disorders that have been studied in those brain regions are listed below each region. Many scRNA-seq studies were also performed on organoids derived from induced pluripotent stem cells (iPSCs) from patients. B.) Cells from either post-mortem brains or organoids are processed for scRNA-seq and the transcriptomes are sequenced. C.) Analysis of scRNA-seq data provides information on dysregulated gene pathways, enriched or depleted cell types, genotype-phenotype correlations, and/or differentially expressed genes in tissue from people suffering from neurobiological disorders.