scRNA-seq of brain cells from 3- and 24-month-old mouse brains

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. Whole brain cells from 3- and 24-month-old female mice were purified for sequencing.小胶质细胞（Microglia）是大脑中重要的免疫细胞。其在衰老过程中会发生一系列特征改变，并增加大脑功能障碍的易感性。然而，目前学界对于衰老进程中小胶质细胞的特征尚未完全明晰。本研究构建了3月龄至24月龄小鼠小胶质细胞的转录组与表观基因组图谱，观察到了意想不到的性别差异，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活化的特征差异。为解析衰老小胶质细胞的功能并排除其他衰老脑细胞的干扰，本研究建立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。借助该模型，我们在未衰老的大脑中成功获得了衰老表型的小胶质细胞，并证实衰老小胶质细胞本身即可导致认知功能衰退。综上，本研究为解析小胶质细胞的衰老进程提供了全面的研究资源，为阐明小胶质细胞维持大脑功能的机制提供了新的视角。本研究对3月龄与24月龄雌性小鼠的全脑细胞进行了纯化以用于测序。