Single-nucleus multiome analysis in the human prefrontal cortex identifies gene expression and cis-regulatory elements associated with aging

Aging is an unavoidable part of life, but gaps still remain in the understanding of age-associated molecular changes within the brain. We generated single-nucleus multiome ATAC plus gene expression profiles in 357 human brain samples from European and African admixed ancestry individuals ranging from 15 to 100 years old. The final dataset consisted of paired transcriptomic and epigenomic profiles for over 1.5 million cells. These were classified into seven major cell types using canonical marker genes, and each type was analyzed for features associated with aging. Open chromatin regions were correlated with transcription factor expression to identify age-associated regulatory networks, and co-accessibility identified linked peaks and genes, revealing a catalog of putative cis-regulatory elements by cell type. These multiomic data serve as a resource to characterize transcriptional regulation by cell type and generate hypotheses about how these distinct profiles both influence and are influenced by aging and disease.