Fujita Yuki, Yamashita Toshihide
Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan.
WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan.
Front Cell Dev Biol. 2021 Jan 21;8:626541. doi: 10.3389/fcell.2020.626541. eCollection 2020.
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.
小胶质细胞是中枢神经系统（CNS）中的常驻免疫细胞。小胶质细胞在形态、密度、电生理特性和基因表达谱方面表现出多样性，并在生理和病理条件下的神经发育及成年期发挥多种作用。最近使用批量和单细胞RNA测序进行的转录组分析表明，小胶质细胞可以在各种情况下改变其基因表达谱，如CNS中的发育阶段、衰老和疾病进展，这表明小胶质细胞的异质性可能与其不同的功能相关。表观遗传变化，包括组蛋白修饰和DNA甲基化，协调基因表达，从而有助于调节细胞状态。在本综述中，我们总结了目前关于小胶质细胞时空和功能多样性背后的表观遗传机制的知识，这些机制会随着发育阶段和疾病状况而改变。我们还讨论了这些知识如何可能推动疾病治疗方法的进展。
