Bulk RNA-seq of microglia at different ages

Microglia are important immune cells in the brain. Microglia undergo a series of alterations during aging and increase the susceptibility to brain dysfunctions. However, the characteristics of microglia during the aging process are not fully understood. In this study, we mapped transcriptional and epigenetic profiles of microglia from 3- to 24-month-old mice. We observed unexpected gender divergences and identified age-dependent microglia (ADEM) genes in the aging process. We then compared characteristics between microglial aging and activation. To dissect the function of aged microglia excluding the influence from other aged brain cells, we established an accelerated microglial turnover model without directly affecting other brain cells. By this model, we achieved aged microglia in non-aged brains and confirmed that aged microglia per se contribute to cognitive decline. Collectively, we provide a comprehensive resource to decode the aging process of microglia, shedding light on how microglia maintain brain functions. Microglia from 3- to 24-month-old female and male mouse brains were purified for RNA sequencing.小胶质细胞（Microglia）是大脑中重要的免疫细胞。该类细胞在衰老过程中会发生一系列改变，并提升大脑功能障碍的易感性。然而，目前学界尚未完全阐明衰老进程中小胶质细胞的特征。本研究对3至24月龄小鼠的小胶质细胞进行了转录组与表观基因组图谱绘制，观察到了未预期的性别差异，并鉴定出衰老过程中的年龄依赖性小胶质细胞（age-dependent microglia, ADEM）基因。随后，本研究对比了小胶质细胞衰老与激活的特征差异。为排除其他衰老脑细胞的干扰以解析衰老小胶质细胞的功能，本研究构建了一种不会直接影响其他脑细胞的小胶质细胞更新加速模型。通过该模型，我们在未衰老的大脑中获得了衰老状态的小胶质细胞，并证实衰老小胶质细胞本身即可导致认知功能衰退。综上，本研究提供了一套可解析小胶质细胞衰老过程的综合性资源，为阐明小胶质细胞如何维持大脑功能提供了新视角。本研究纯化了3至24月龄雌雄小鼠大脑中的小胶质细胞以进行RNA测序。