Extended Data Fig. 2: Aged and RISP-cKO microglia have distinct transcriptional profiles.
Survival curves for (a) Males RISP-cHET (n = 5), RISP-cKO (n = 14) and (b) Females RISP-cHET (n = 11) and RISP-cKO (n = 22). (c) Normalized enrichment score from GSEA analysis of DAM, ISR, Hallmark Interferon Alpha Response and Hallmark TNF-α signialing via NF-κB comparing RISP-cKO n = 10 (M = 7, F = 3) and RISP-cHET 2-year-old n = 3 (M = 1, F = 2) to 1yr RISP-cHET n = 9 (M = 7, F = 2). (d) Venn Diagram comparing upregulated genes in RISP-cKO 1yr and RISP-cHET 2yr microglia from the DAM gene expression module. Enrichment score vs gene rank histograms of DAM modules in (e) RISP-cKO 1yr vs RISP-cHET 1yr and (f) RISP-cHET 2yr vs RISP-cHET 1yr. (g) Venn Diagram comparing upregulated genes in RISP-cKO 1yr and RISP-cHET 2yr microglia from the ISR gene expression module. Enrichment score vs gene rank histograms of ISR modules in (h) RISP-cKO 1yr vs RISP-cHET 1yr and (i) RISP-cHET 2yr vs RISP-cHET 1yr. Enrichment score vs gene rank histograms of Hallmark Interferon-α Response (MM3877) module in (j) RISP-cKO 1yr vs RISP-cHET 1yr and (k) RISP-cHET 2yr vs RISP-cHET 1yr. Enrichment score vs gene rank histograms of Hallmark Interferon-α Response (MM3877) module in (l) RISP-cKO 1yr vs RISP-cHET 1yr and (m) RISP-cHET 2yr vs RISP-cHET 1yr. (n) Percent of total time in center of open-field test conducted on 1-year-old RISP-cHET (n = 6) RISP-cKO (n = 11) and 2-year-old RISP-cHET (n = 6) mice. (o) Rotarod test of 1-year-old Het (n = 7), 1-year-old RISP-cKO (n = 16) and 2-year-old RISP-cHET (n = 10) mice. In a and b we used Kaplan-Meier tests with Manetl-Cox logrank and Gehan-Breslow-Wilcoxon test adding extra weight for early time points. In c-m enrichment analysis was then performed for all gene sets simultaneously using the ‘fgseaMultilevel’ method using gene-level Wald statistics as rankings and default parameters. For n and o we performed a one-way ANOVA with a Dunnett’s multiple comparisons test with a single pooled variance.
