Fig. 2
The protein signature of activated mouse microglia is comparable with hiMGL and associates well between mouse CSF and the hiMGL secretome. (A-B) Comparing upregulated proteins (red) versus downregulated proteins (blue) with significant changes indicated as colored dots, in the proteome of iPSC-derived microglia (hiMGL) with the following genotypic comparisons: (A) GRN ko / WT and (B) TREM2 ko / WT. (C-D) Comparing proteomic changes in conditioned media from hiMGL (secretome) with the following genotypic comparisons: (C) GRN ko / WT (D) TREM2 ko / WT. Cathepsins, as well as APOE and LGALS3 are marked in yellow. Other proteins of interest are marked in green. Selected cut-off values: p-value < 0.05 (colored dots) and − 0.5 > Log2 FC > 0.50 (filled dots). The -log10 transformed p-value of each protein is plotted against its log2 fold change. (E) Marker proteins related to microglia activation showed significant consistency between the proteome (first and third column) and transcriptome (second and fourth column) in hiMGL cell lysates. mRNA data were obtained by qPCR. (F) Proteins significantly (p-value < 0.05) upregulated in lysates of hiMGL GRN ko (pink) and Grn ko mice (orange). 150 proteins were significantly upregulated in both models (a selection of overlapping proteins is shown in the box). (G) Proteins significantly (p-value < 0.05) upregulated in the conditioned media of GRN ko hiMGL (pink) and CSF sampled from 12 months old Grn ko mice (orange). 20 proteins were significantly upregulated in both mouse CSF and conditioned media of hiMGL (box). Statistical differences were calculated using Student’s t-test. * = p-value < 0.05, ** = p-value < 0.01, *** = p-value < 0.001; n.s. = non-significant. False discovery rate (FDR) was not considered for the presented visualizations. All presented proteomic data were obtained by LC-MS/MS. Proteomic data were generated from hiMGL using the following experimental groups: n (GRN ko cell lysate) = 6, n (TREM2 ko cell lysate) = 6, n (WT cell lysate) = 6, n (GRN ko conditioned media) = 6, n (TREM2 ko conditioned media) = 6; n (WT conditioned media) = 6