Abstract Understanding the exact cell-type composition in the different regions of the human brain is a fundamental step when trying to integrate physiological, behavioral, neurochemical and molecular data. At present, although major categories of cell-types present in the human brain have been defined through a handful of specific markers, the different subtypes within these categories as well as their location are far from understood. Cytosine DNA methylation (mC) is a stable epigenomic signature that persists in post-mitotic cells throughout their lifetime, defining their cellular identity. Open chromatin marks gene regulatory elements that control cell type-specific gene expression patterns. Single cell DNA methylation and open chromatin profiles have been successfully used to identify de novo distinct cell types in heterogeneous tissues including the brain. This U01 aims to produce a first version of an epigenomic cell atlas at the single-cell level across the human brain. Multi-modal integration between epigenomic and transcriptomic signatures will allow the identification of new cell types and unique cell-type markers that will become available to the community. Epigenomic profiling of human brain cells permits the discovery of cell type-specific regulatory regions, which will facilitate the functional analysis of genetic variants associated with psychiatric and neurological disorders.