We generated more that 120,000 single-nuclei RNA-seq profiles and identified 11 neuronal and six glial cell types; these included known subtypes of excitatory neurons and interneurons, main types of glial cells and brain endothelial cells. To identify genes dysregulated in ASD in a cell type-specific manner, we compared nuclei profiles from ASD samples and control subjects. In total, we identified 707 differentially expressed genes (DEGs); 81% of these genes were differentially expressed in a single cell type.
Our findings show that development and synaptic signaling of upper-layer excitatory neurons is especially affected in ASD. Moreover, we find significant dysregulation of grey matter astrocyte-encoded genes responsible for astrocyte development and cell-cell signaling. These findings indicate molecular pathological changes in upper-layer cortical neuron circuits and aberrant astroglia-neuronal interactions in ASD and identify potential cellular and molecular therapeutic targets.
Direct cell browser link: autism.cells.ucsc.edu