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Microglia are resident immune cells in the central nervous system (CNS). Microglia exhibit diversity in their morphology, density, electrophysiological properties, and gene expression profiles, and play various roles in neural development and adulthood in both physiological and pathological conditions. Recent transcriptomic analysis using bulk and single-cell RNA-seq has revealed that microglia can shift their gene expression profiles in various contexts, such as developmental stages, aging, and disease progression in the CNS, suggesting that the heterogeneity of microglia may be associated with their distinct functions. Epigenetic changes, including histone modifications and DNA methylation, coordinate gene expression, thereby contributing to the regulation of cellular state. In this review, we summarize the current knowledge regarding the epigenetic mechanisms underlying spatiotemporal and functional diversity of microglia that are altered in response to developmental stages and disease conditions. We also discuss how this knowledge may lead to advances in therapeutic approaches for diseases.

Alterations in Chromatin Structure and Function in the Microglia