Fig 1: TREM2 knockout decreases phagocytosis of disease-relevant stimuli.a Isogenic TREM2 WT and KO microglia were exposed to recombinant APOE 2 (green), APOE 3 (yellow), APOE4 (red), or a vehicle control (blue). Images were taken every hour for 24 h with IncuCyte S3 live imaging system. Scale bar: 200 µm. Statistical differences were quantified at 24 h (right, n = 3 independent wells with 4 images per well. Table (right) shows difference between WT and KO lines for each APOE genotype replicated in 2 isogenic backgrounds; two-way ANOVA, Tukey post hoc test, multiple comparisons. WT(veh) vs WT(APOE2): p = 0.0052, WT (APOE2) vs KO (APOE2): p = 0.0075, ****p < 0.0001, ns: p > 0.8.) Data are represented as mean values ± SEM. Microglia were exposed to b recombinant APOE3 (red), c fibrillar fluorescent beta-amyloid (green), d pHrodo-labeled human synaptosomes (green), or e pHrodo-labeled Zymosan A (red). Left shows representative images at 24 h. Inner graphs show untreated cells and the relative effects of TREM2 deletion alone on phagocytosis, or with addition of a SYK inhibitor (5 µM R406). Statistical differences were quantified at 24 h (right). For all panels, n = 3–4 independent wells with 4 images per well; two-way ANOVA, Tukey post hoc test, multiple comparisons. b ***p = 0.0002, ****p < 0.0001, ns p = 0.998 c *p = 0.0393, ****p < 0.0001 d ***p = 0.0008, ****p < 0.0001, ns p = 0.7912 e WT vs WT + R406 p = 0.301, KO vs KO + R406 p = 0.320, WT vs KO p = 0.344. Data are represented as mean values ± SEM. Experiments were replicated in three isogenic lines with equivalent results.