As extremely sensitive immune cells, microglia act as versatile watchdogs of the central nervous system (CNS) that tightly control tissue homeostasis. Therefore, microglial activation is an early and easily detectable hallmark of virtually all neuropsychiatric, neuro-oncological, neurodevelopmental, neurodegenerative and neuroinflammatory diseases. The recent introduction of novel high-throughput technologies and several single-cell methodologies as well as advances in epigenetic analyses helped to identify new microglia expression profiles, enhancer-landscapes and local signaling cues that defined diverse previously unappreciated microglia states in the healthy and diseased CNS. Here, we give an overview on the recent developments in the field of microglia biology and provide a practical guide to analyze disease-associated microglia phenotypes in both the murine and human CNS, on several morphological and molecular levels. Finally, technical limitations, potential pitfalls and data misinterpretations are discussed as well.

作为极其敏感的免疫细胞，小胶质细胞可作为中枢神经系统 (CNS) 的多功能看门狗，严格控制组织稳态。因此，小胶质细胞激活是几乎所有神经精神、神经肿瘤、神经发育、神经退行性和神经炎性疾病的早期且易于检测的标志。最近引入的新的高通量技术和几种单细胞方法以及表观遗传分析的进步有助于确定新的小胶质细胞表达谱、增强子景观和局部信号线索，这些信号定义了健康和患病中枢神经系统中以前未被重视的各种小胶质细胞状态. 这里，我们概述了小胶质细胞生物学领域的最新发展，并为分析小鼠和人类 CNS 中与疾病相关的小胶质细胞表型提供了实用指南，在几个形态学和分子水平上。最后，还讨论了技术限制、潜在陷阱和数据误解。