An environment-dependent transcriptional network specifies human microglia identity


We used RNA sequencing, chromatin immunoprecipitation sequencing, and assay for transposase-accessible chromatin sequencing to characterize the transcriptomes and epigenetic landscapes of human microglia isolated from surgically resected brain tissue in excess of that needed for diagnosis. Although some effects of underlying disease cannot be excluded, the overall pattern of gene expression was markedly consistent. Microglia-enriched genes were found to overlap significantly with genes exhibiting altered expression in neurodegenerative diseases and psychiatric disorders and with genes associated with a wide spectrum of disease-specific risk alleles. Human microglia gene expression was well correlated with mouse microglia gene expression, but numerous species-specific differences were also observed that included genes linked to human disease. More than half of the genes associated with noncoding GWAS risk alleles for Alzheimer's disease are preferentially expressed in microglia.