Single-cell transcriptome analysis of wildtype, TREM2 knockout, GPR34 knock-out or TREM2/GPR34 double knock-out primary microglia from wildtype and APP knock-in mice (8 months)

Microglia are broadly implicated in modifying disease risk in the central nervous system (CNS). Identifying regulators of microglia state is critical for elucidating their role in disease and identifying novel drug targets. GPR34 is a G-protein coupled receptor expressed in homeostatic microglia where its function is not well understood. Like TREM2, GPR34 detects lipid ligands. In both healthy and amyloid mouse models, Gpr34 KO accelerated microglial state transcriptionally and histologically consistent conversion of homeostatic microglia to a disease-associated microglia (DAM) state. Shifts in microglial state were accompanied by increased expression of multiple metabolic gene sets.