Fig. 3

A Volcano plot presentation of the differently expressed transcripts between wildtype vs. Grn^−/− (left panel), Grn^−/− vs. Grn^−/− × Tmem106b^T186S/T186S and wildtype vs Grn^−/− × Tmem106b^T186S/T186S mice (n = 4, each genotype) in RNA isolated from 6-month-old mice. The thresholds for transcripts reaching statistically significant differences (fold change (fc) < − 1.5 / > 1.5; p < 0.05) are indicated (dotted lines), and the quadrants with transcripts reaching the threshold are colored in green. Grn as the top-down-regulated transcript in Grn^−/− and Grn^−/− × Tmem106b^T186S/T186S mice was excluded in the volcano-plot representation. B Principal component analysis (PCA) of the 12 total brain samples analyzed by Nanostring nCounter “Glia Profiling” panel. Every individual point represents one individual biological replicate: Wildtype = black, Grn^−/− = green Grn^−/− × Tmem106b^T186S/T186S = red. Note that the wildtype group can be clearly separated from the other two groups, while there is an overlap between Grn^−/− and Grn^−/− × Tmem106b^T186S/T186S. C Fold changes of the top 14 transcripts differentially expressed between wildtype and Grn^−/− mice determined by NanoString nCounter analysis. Statistics indicate significant differences between wildtype and Grn^−/− / wildtype and Grn^−/− × Tmem106b^T186S/T186S mice. For non of the selected genes, any significant differences were found between Grn^−/− and wildtype and Grn^−/− × Tmem106b^T186S/T186S. *p < 0.05; **p < 0.01; ***p < 0.001; ns = not significant; (n = 4, each genotype). D Heatmap of 86 gene transcripts analyzed by NanoString nCounter analysis in wildtype, Grn^−/−, Grn^−/− × Tmem106b^T186S/T186S mice (n = 4, each genotype) from total brain RNA isolated from 6-month-old mice. The expression-corrected and housekeeping gene-normalized RNA counts for each gene and sample were normalized to the mean value of the wildtype animals. Grn was excluded from this representation. E Pathway enrichment of differentially expressed genes (p < 0.01) between wildtype and Grn^−/− mice (upper panel) and wildtype and Grn^−/− × Tmem106b^T186S/T186S mice (lower panel) by the “Enrichr” tool. The top-enriched terms of the gene ontology term “Cellular Component 2021” are depicted