Cortical single-cell RNA sequencing of the microglia specific TREM2 inducible mouse models in the middle stage of amyloid deposition

We induced TREM2 expression at 2 months of age in our 5xFAD/TREM2 mouse models and harvested the animals at 5 months of age. The single cells from the cortex were isolated and subjected to the single-cell RNA seq to investigate the effects of TREM2 on microglia transcriptomic profiles in the middle stage of amyloid development. Our data showed that TREM2-WT induced the mTOR/EIF2 signaling pathways and restricted the disease associated microglia (DAM) signature. In contrast TREM2-R47H variant significantly upregulated the MHC class II molecules, enriched the antigen presentation pathway, and exacerbated a signature of antigen presentation contributing to enhanced amyloid pathology. Overall design: Six mice (3 males and 3 females) were analyzed for each of the four groups, including 5xFAD/TREM2-WT-Ctrl, 5xFAD/TREM2-WT-Induced, 5xFAD/TREM2-R47H-Ctrl, 5xFAD/TREM2-R47H-Induced .