Abstract

Autism Spectrum Disorders (ASD) are clinically and genetically heterogeneous. Nevertheless, a characteristic gene expression signature in postmortem cortex is shared across most ASD cases. Knowing whether this signature reflects changes in cells of particular types would help to determine the molecular, cellular, and anatomical etiology of ASD. To investigate we took advantage of cell type marker genes defined by recent single cell transcriptome sequencing from mouse or human cortex. We find that microglial markers showed significantly and substantially higher median expression in postmortem ASD than in control cortex for both mouse and human markers (21% higher for orthologous markers defined in mouse; 93% higher for human markers). In contrast, neuronal markers showed reduced median expression: 12% and 16% lower for mouse interneurons and pyramidal neurons, 40% lower for human neurons, and 36% lower for a class of human excitatory projection neurons. Cell type density alterations in ASD brains are indicated because distributions of these cell type markers are shifted concordantly. Importantly, orthologous mouse neuronal marker genes encoding proteins localized to diverse neuronal compartments all showed reduced median expression in ASD. Our results provide a framework for revealing the basis of transcriptomic differences in ASD. We propose comparing cell type density alterations in post-mortem tissue with and without these distinctive gene expression changes to reconcile results from stereological and transcriptomic studies.