Transcriptome analysis reveals dysregulation of innate immune response genes and neuronal activity-dependent genes in autism

作者：Simone Gupta, Shannon Ellis, Foram N. Ashar, Anna Moes, Joel S. Bader, Jianan Zhan, Andrew B. West, Dan E. Arking · 发表于：Nature Communications · 年份：2014 · DOI：10.1038/ncomms6748 · 被引用次数：548 · 研究领域：RNA regulation and disease、Genetics and Neurodevelopmental Disorders、Autism Spectrum Disorder Research

Recent studies of genomic variation associated with autism have suggested the existence of extreme heterogeneity. Large-scale transcriptomics should complement these results to identify core molecular pathways underlying autism. Here we report results from a large-scale RNA sequencing effort, utilizing region-matched autism and control brains to identify neuronal and microglial genes robustly dysregulated in autism cortical brain. Remarkably, we note that a gene expression module corresponding to M2-activation states in microglia is negatively correlated with a differentially expressed neuronal module, implicating dysregulated microglial responses in concert with altered neuronal activity-dependent genes in autism brains. These observations provide pathways and candidate genes that highlight the interplay between innate immunity and neuronal activity in the aetiology of autism.