Single cell ATAC-seq identifies broad changes in neuronal abundance and gene regulation in Down Syndrome

To characterize cellular and molecular changes associated with Down Syndrome, we performed single-cell combinatorial indexing assay for transposase accessible chromatin using sequencing (sci-ATAC-seq) on cortices of adult Ts65Dn mice and control littermates. Analyses of 13,766 cells revealed 26 classes of cells in the cortices of both genotypes. The most abundant cells, a class of excitatory neurons, was reduced by (~17 %) in Ts65Dn mice; three of the four most common classes of interneurons were increased, with a total increase of ~50 % of all interneurons. Ts65Dn mice display changes in accessibility at motifs of transcription factors encoded within the triplicated locus, and those that are determinants of neuronal lineage. Overall design: sci-ATAC-seq on 2n and Ts65dn cortex