A temporal cortex cell atlas highlights gene expression dynamics during human brain maturation

Abstract

The human brain undergoes protracted postnatal maturation, guided by dynamic changes in gene expression. Most studies exploring these processes have used bulk tissue analyses, which mask cell-type-specific gene expression dynamics. Here, using single-nucleus RNA sequencing on temporal lobe tissue, including samples of African ancestry, we build a joint pediatric and adult atlas of 75 cell subtypes, which we verify with spatial transcriptomics. We explore the differences between pediatric and adult cell subtypes, revealing the genes and pathways that change during brain maturation. Our results highlight excitatory neuron subtypes, including the LTK and FREM subtypes, that show elevated expression of genes associated with cognition and synaptic plasticity in pediatric tissue. The resources we present here improve our understanding of the brain during its development and contribute to global efforts to build an inclusive brain cell map. This Pediatric Cell Atlas study analyzes temporal cortex single-nucleus RNA sequencing datasets from eight diverse donors from 4 to 50 years of age, describing gene expression dynamics over the course of brain maturation.