Transcriptomic Evolution of Neuronal Cell Classes and Cell Types in Human, Chimpanzee, and Rat

The primary (M1) motor cortex is a highly conserved part of the mammalian brain, responsible for the direct control of voluntary muscles. While it is known that different species have differently structured motor cortices due to their unique needs and evolution, there is little knowledge about the cross-species differences between motor cortex cell types at the molecular level, and no comparison of humans and our closest living relatives, chimpanzees. A cross-species molecular level understanding of the M1 cortex would reveal the development of specific cell types and genes in line with evolutionary progression in motor skills. Using single nucleus RNA sequencing (snRNA-seq) on samples gathered from humans, chimpanzees, and rats, this research identified over 50 excitatory neuron cell types in three species, along with differences in celltype/subclass proportions, marker genes, and some potentially unidentified cell types. These results suggest the existence of Layer 4-like excitatory neurons in primates. Additionaly, differentially overexpressed genes of human specific cell types were enriched in pathways implicated in ADHD, autism, and other human diseases.