TREM2 regulates microglial lipid metabolism during aging in mice [RNA-Seq]

TREM2 is a microglial-specific gene implicated in late-onset Alzheimer's Disease (AD). Recent studies have identified that Trem2-deficient mice exhibit transcriptional changes in microglial gene expression that minimize the upregulation of lipid metabolism and lysosomal genes in AD disease models. We detect similiarly attenuated expression of lipid metabolism genes in microglia isolated from brains of aged Trem2 knockout mice. Microglia and astrocytes were purified from brains of Trem2 wildtype and homozygous knockout mice of young (2 months) and old (16-18 months) mice using fluorescent activated cell sorting (FACS). Gene expression was assessed using 3' tag sequencing of poly-adenylated RNA (QuantSeq, Lexogen, Vienna, Austria) with unique-molecular identifiers (UMIs).TREM2是一种与晚发性阿尔茨海默病（AD）相关的小胶质细胞特异性基因。近期研究表明，在阿尔茨海默病疾病模型中，TREM2缺陷小鼠的小胶质细胞基因表达出现转录组改变，可抑制脂质代谢与溶酶体相关基因的上调。我们在从老年TREM2敲除小鼠脑组织中分离的小胶质细胞内，检测到了类似的脂质代谢基因表达减弱现象。本研究通过荧光激活细胞分选术（FACS），分别从年轻（2月龄）与老年（16-18月龄）的TREM2野生型及纯合敲除小鼠的脑组织中纯化小胶质细胞与星形胶质细胞。采用带有唯一分子标识符（UMIs）的聚腺苷酸化RNA的3'端标签测序技术（QuantSeq，Lexogen公司，奥地利维也纳）对基因表达水平进行检测。