No brain no gain: single-cell RNA sequencing in the study of brain tissue

Abstract

Single-cell RNA sequencing (scRNA-seq) technology is applied in molecular biology to quantify and analyze gene expression of individual cells present in a tissue sample. During the last 14 years, the technology underwent an exponential evolution towards automation and high- throughput. Current platforms enable the simultaneous analysis of hundreds of thousands of cells, requiring large computational power to analyze the sequencing data output and increased complexity of data-processing. However, scRNA-seq contribution to tissue heterogeneity characterization outweighs its high technical demands, especially in the study of the brain. ScRNA-seq application in human samples and animal models has been reviewed several times, but no review collects the contribution of scRNA-seq technology applied to in vitro models in the study of the human brain development, aging and associated diseases. This review compiles a representative collection of publications with scRNA-seq data application in in vitro brain models. It demonstrates that scRNA-seq data alone or in combination with other single-cell omics has proven useful to validate fidelity and reproducibility of in vitro models of the human brain, as well as for the identification of novel cell types or gene expression signatures associated with neurodevelopmental or neurodegenerative disorders. Single-cell transcriptomics are still in development, but hold a great potential in future research in developmental biology and translational medicine.