Fig. 6: Transcriptome-wide impact of Akap11 deficiency across ages, brain regions and cell types.

a Schematic of brain regions collected for RNA sequencing. b Number of differentially expressed genes (DEGs) in bulk RNA sequencing across brain regions and ages. Experiments are n = 4 to 6 per condition (see Methods). Area of circles represents DEG counts, defined by FDR adjusted P-values < 0.05, for Akap11 mutants compared to WT controls. Two-tailed Wald test, with B-H FDR correction. c GSEA of bulk RNA sequencing, showing MsigDB pathways of interest, genes associated with psychiatric and neurological conditions by GWAS^12,83, and a curated set of activity-regulated genes⁸⁰. Black outline indicates FDR < 0.05 significance. GSEA uses a Kolmogorov-Smirnov test, two tailed, with B-H FDR correction applied. d Schematic of snRNA-seq experiments in PFC and striatum, with UMAP plots of major cell types identified at 12w by snRNA-seq. Experiments are n = 4 per condition, with the exception of 12w Str, with n = 5 WT. e Number of DEGs in snRNA-seq experiments, defined by having an FDR adjusted P-value < 0.05. Comparisons were calculated using two-tailed likelihood ratio test, which were FDR corrected with B-H adjustment. f Heatmap showing Log₂FC values for a selection of neuromodulation-related genes, plotted across transcriptomics, proteomics, and phosphoproteomics measurements. Genes indicated in the phosphoproteomics columns reflect the most significantly changed phosphosite per gene. P < 0.05 proteins and FDR < 0.05 transcripts are outlined with a black box.