TREM2 regulates microglial cholesterol metabolism upon chronic phagocytic challenge [bulk 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 find that chronic phagocytic challenge from demyelination generates similiarly attenuated expression of lysosomal and lipid metabolism genes in microglia isolated from Trem2 knockout mouse brain. Trem2 wildtype, heterozyogus knockout, and homozygous knockout mice were fed a control or 0.2% cuprizone diet for 5 weeks or 12 weeks to generate acute or chronic demyelination, respectively. Microglial and pooled non-microglial cell type gene expression was assessed using 3' tag sequencing of poly-adenylated RNA (QuantSeq, Lexogen, Vienna, Austria).