Significant Evolutionary Constraints on Neuron Cells Revealed by Single-Cell Transcriptomics

Recent advances in single-cell RNA-sequencing technology have enabled us to characterize a variety of different cell types in each brain region. However, the evolutionary differences among these cell types remain unclear. Here, we analyzed single-cell RNA-seq data of >280,000 cells and developmental transcriptomes of bulk brain tissues. At the single-cell level, we found that the evolutionary constraints on the cell types of different organs significantly overlap with each other and the transcriptome of neuron cells is one of the most restricted evolutionarily. In addition, mature neurons are under more constraints than neuron stem cells as well as nascent neurons and the order of the constraints of various cell types of the brain is largely conserved in different subregions. We also found that although functionally similar brain regions have comparable evolutionary constraints, the early fetal brain is the least constrained and this pattern is conserved in the mouse, macaque, and humans. These results demonstrate the importance of maintaining the plasticity of early brain development during evolution. The delineation of evolutionary differences between brain cell types has great potential for an improved understanding of the pathogenesis of neurological diseases and drug development efforts aimed at the manipulation of molecular activities at the single-cell level.