Figure 7. The transcript profile of the CC founder strains matches that of both CKD and AKI at week 1, while the PWK/PhJ and C57BL/6J strains match CKD at 6 weeks.

(A) Schematic of the approach. Gene expression signatures of human kidney diseases were obtained from public repositories (see Supplemental Table 2) and then compared with the mouse differentially expressed genes upon folic acid treatment. Both human and mouse data sets used a differentially expressed genes (DEGs) cutoff of |log₂(fold change)| > 0.5 and FDR-corrected P < 0.05. Transcripts were considered overlapping if they varied in the same direction in mice and humans. Overlap percentage is “number overlapped transcripts”/“maximum possible overlap”, where the maximum possible overlap is the number of human and mouse DEGs — whichever is smallest. For each overlap, we performed a GSEA (see Supplemental Figure 8). (B) Overlap plot at week 1, exact numbers are indicated within each tile. Human kidney diseases overlap strongly with the response to folic acid in mice. This concordance was lost in most strains at week 6, except in the PWK/PhJ and C57BL/6J, which retained a large overlap (~20% genes) with human chronic kidney diseases. (C and D) Pie charts of selected significant gene sets among upregulated (C) or downregulated (D) transcripts. The size of each pie chart is log-proportional to the number of overlapped genes. The greatest overlaps involved an upregulation of immune-related transcripts and extracellular matrix components and a downregulation of mitochondrial and metabolic transcripts. This indicates a strong similarity between fibrogenesis, immune, and metabolic pathways implicated in mice and humans. At week 6, the inflammatory signature in the PWK/PhJ and C57BL/6J strains was similar to chronic human diseases but lost their similarities with acute kidney disease.