Single-Cell Profiling of DNA Methylation in Autism Spectrum Disorder Prefrontal Cortex Reveals Distinct Regulatory and Aging Signatures

Autism spectrum disorder (ASD) is a prevalent and heterogeneous condition that profoundly impacts health and behavior. Analysis of gene expression in the cortex broadly implicates decreased synaptic functioning in excitatory neurons and increased reactivity in glia in ASD; however, whether these phenotypes are reflected in epigenetic signatures is unknown. Here, we report on the first single-cell analysis of DNA methylation (DNAm) in ASD. We profile DNAm from over 60,000 nuclei derived from 49 donors and interpret our findings with gene expression from the same nuclei using snmCT-seq.