Fig. 4

Transcriptomic profiling and WGCNA analysis of the ACSS2 upregulation in middle-aged 5 × FAD mice. A-C Transcriptomic profile of dorsal hippocampus from mice with ACSS2 upregulation. The volcano plot for differentially expressed genes (DEGs) (FDR < 0.05 and |fold change|≥ 1.2) in WT-GFP vs. FAD-GFP (A, left panel), FAD-GFP vs. FAD-ACSS2(A, right panel). Red plots represent upregulated DEGs. Blue plots represent downregulated DEGs. Gray points represent non-DEGs. n = 3 per group (A). Correlation analysis of fold change between WT-GFP vs. FAD-GFP and FAD-GFP vs. FAD-ACSS2 for genes with |fold change|≥ 1.2 (each gene corresponds to one point). The red dots denote genes that were downregulated (upregulated) in 5 × FAD mice which were upregulated (downregulated) by ACSS2 upregulation (B). KEGG pathway analysis for the DEGs between WT-GFP and FAD-GFP group, with the top 10 pathways shown (C, top panel). The top 10 pathways that were altered by ACSS2 upregulation in 5 × FAD mice (C, bottom panel). D, E WGCNA analysis of ACSS2 upregulation in 5 × FAD mice. Modules associated with the comparison of FAD-ACSS2 with FAD-GFP mice (n = 3 per group) (D). Numbers in the heatmap show the correlation coefficient. Modules with positive values (red) indicate an upregulation in FAD-ACSS2 vs. FAD-GFP mice; modules with negative values (blue) indicate a down-regulation. Network plot of the top 10 genes with the highest intramodular connectivity (hub genes) in the brown module (E, top panel). Gene ontology (GO) term enrichment of the brown module using 1086 module genes (E, middle panel). The orange line indicates the threshold of significance (P = 0.05). The trajectory of the module eigengenes (MEs) for each transcript in the brown module between FAD-ACSS2 and FAD-GFP mice (E, bottom panel). Data are expressed as mean ± SEM. Statistical significance was calculated by unpaired two-tailed t-test (E, bottom). ** P < 0.01