Single-cell transcriptomics as a framework and roadmap for understanding the brain

Abstract

A framework for interpreting and guiding experimental examination of the brain is essential for neuroscience. Recently, single-cell RNA sequencing and single-molecule fluorescent in situ hybridization have emerged as key technologies to generate such a framework at a single-cell resolution. These technologies provide a powerful complement for understanding gene expression in the brain: RNA sequencing enables genome-wide high-throughput quantification of gene expression, and in situ hybridization yields spatial registration of gene expression at a cellular resolution. Here, I discuss the insight that each of these technologies individually provide, and how they can be paired in principle and practice to resolve the cell-type-specific spatial organization of the brain. I further discuss the potential of cutting-edge spatial transcriptomics technologies that leverage the advantages of both techniques within the same assay, as well as how transcriptomic assays can be linked with higher-order features of brain structure and function. Such current and forthcoming transcriptomic technologies will have immense impact in generating an underlying logic of the nervous system, and will guide experiments and interpretations across molecular, cellular, circuit, and behavioural neuroscience.

Keywords: Cell type; Gene expression; Single-cell RNA sequencing; Single-molecule fluorescent in situ hybridization; Spatial transcriptomics; Transcriptome.