Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain

TLDR

Single‑nucleus gene expression profiling enables deeper understanding of human brain cellular diversity. The authors developed a single‑nucleus sequencing method applied to Brodmann‑area cells from a postmortem brain. Clustering revealed 16 neuronal subtypes with regional excitatory and inhibitory variations that align with Brodmann areas, demonstrating the method’s potential for broad disease‑related brain sampling. Published in Science (p.

Abstract

Single-nucleus gene expression Identifying the genes expressed at the level of a single cell nucleus can better help us understand the human brain. Blue et al. developed a single-nuclei sequencing technique, which they applied to cells in classically defined Brodmann areas from a postmortem brain. Clustering of gene expression showed concordance with the area of origin and defining 16 neuronal subtypes. Both excitatory and inhibitory neuronal subtypes show regional variations that define distinct cortical areas and exhibit how gene expression clusters may distinguish between distinct cortical areas. This method opens the door to widespread sampling of the genes expressed in a diseased brain and other tissues of interest. Science , this issue p. 1586