GSE173650
An Atlas of Gene Regulatory Elements in Adult Mouse Cerebrum
The mammalian cerebrum performs high-level sensory, motor control and cognitive functions through highly specialized cortical networks and subcortical nuclei. Recent surveys of mouse and human brains with single cell transcriptomics and high-throughput imaging technologies have uncovered hundreds of neuronal cell types and a variety of non-neuronal cell types distributed in different brain regions, but the cell-type-specific transcriptional regulatory programs responsible for the unique identity and function of each brain cell type have yet to be elucidated. Here, we probe the accessible chromatin in >800,000 individual nuclei from 45 regions spanning the adult mouse isocortex, olfactory bulb, hippocampus, and cerebral nuclei, and use the resulting data to map the state of 491,818 candidate cis regulatory DNA elements (cCREs) in 160 distinct sub-types. We find high specificity of spatial distribution for not only excitatory neurons, but also most classes of inhibitory neurons and a subset of glial cell types. We characterize the gene regulatory sequences within these cell types that underlie their regional specificity. We further link a significant fraction of the cCREs to putative target genes expressed in diverse cerebral cell types and uncover transcriptional regulators involved in a broad spectrum of molecular and cellular pathways in different neuronal and glial cell populations. Our results provide a foundation for comprehensive analysis of gene regulatory programs of the mammalian brain and assist in the interpretation of non-coding risk variants associated with various neurological diseases and traits in humans. To facilitate the dissemination of information, we have set up a web portal (http://catlas.org/mousebrain). Overall design: Additional single nuclei ATAC-seq with two replicates.