Single-nucleus RNA-sequencing anslysis of PFC from human.

Brain aging is accompanied by a decline and loss of cognitive and learning memory, and is associated with many neurodegenerative diseases, thus posing a significant threat to global health. There are no systematic studies on the single-cell level of human brain aging to explain cell-specific transcriptomic changes. Here, by integrating two independent single-nucleus transcriptome sequencing (snRNA-seq) data of human prefrontal cortex tissue, we found that the prefrontal cortex has highly cellular heterogeneity during aging. The findings showed significantly reduced excitatory neurons during aging in healthy individuals. However, the number of microglia and oligodendrocytes were significantly increased. We compared levels of gene expression in cells across all stage by cell type, and identified 93 unique differentially expressed genes (DEGs) that implicated all major cell types. All or most of DEGs in oligodendrocyte, OPC, microglia, excitatory, and inhibitory neurons were downregulated, whereas most DEGs in astrocytes, and endotheliocyte were upregulated.