Single Cell Analysis of Gene Regulatory Elements in the Mouse Brain


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The mammalian brain consists of hundreds of cell types that work together to carry out the diverse neurological functions. To understand how neuro circuits form and how their functions are supported by various non-neuronal cell types, it is important to identify and characterize the cis-regulatory sequences in each cell type. Here, we employed a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin (sci-ATAC-seq) to profile chromatin accessibility in more than 1,000,000 cells from 26 cortical and subcortical regions of the rostral mouse brain. The resulting chromatin accessibility maps reveal 125 cellular taxonomy in the neocortex, olfactory bulb, hippocampus, basal ganglia and striatum, and delineate highly cell-type specific usage of ~350k potential regulatory DNA elements. Further integrative analysis uncovers transcription factor networks involved in each cell type, and potential cell types involved in human neurological disease. This rich resource of chromatin accessibility in the mouse brain at single cell resolution lays the foundation for understanding the gene regulatory program in the mammalian brain.