Gene expression profile at single cell level of microglia from forced microglia turnover and control mouse brain

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. Overall design: After 3 rounds of PLX5622-CD diet treatment (3xDR), microglia were purified for sequencing.

小胶质细胞（Microglia）是大脑中重要的免疫细胞。在衰老过程中，小胶质细胞会发生一系列改变，并提升大脑功能障碍的易感性。然而，学界对衰老进程中小胶质细胞的特征仍未完全阐明。本研究对3月龄至24月龄小鼠的小胶质细胞进行了转录组与表观基因组谱的绘制，观察到了未被预见的性别差异，并在衰老过程中鉴定出了年龄依赖性小胶质细胞（ADEM）基因。随后我们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，我们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。借助该模型，我们在非衰老大脑中获得了衰老小胶质细胞，并证实衰老小胶质细胞本身即可导致认知功能衰退。综上，本研究提供了一套用于解析小胶质细胞衰老进程的综合性资源，为阐明小胶质细胞如何维持大脑功能提供了新的见解。实验设计概要：经3轮PLX5622-CD饲料处理（3xDR）后，纯化小胶质细胞并进行测序。