A comparative atlas of single-cell chromatin accessibility in the human brain

Recent advances in single cell transcriptomics illuminate the diverse neuronal and glial cell types within the human brain. However, the regulatory programs governing cell identity and function remain unclear. Using single nucleus ATAC-seq analysis, we explore open chromatin landscapes across 1.1 million cells in 42 brain regions from three adults. Integrating this data unveils 107 distinct cell types and their specific utilization of 544,735 candidate cis-regulatory DNA elements (cCREs) in the human genome. Nearly 1/3 of the cCREs demonstrate conservation and chromatin accessibility in the mouse brain cells. We reveal strong links between specific brain cell types and neuropsychiatric disorders including schizophrenia, bipolar disorder, Alzheimer's disease, and major depression, and develop deep learning models to predict regulatory roles of non-coding risk variants in these disorders.