Fig. 2: Rnf43 and Znrf3 (R&Z) null hepatocytes present lipid metabolic transcriptional changes.
a–f Liver tissues from 1- 3- and 7-month-old R&Zdel mice and R&Zflox littermates were collected and processed for RNAseq analysis. Differentially expressed (DE) gene profiles were obtained as described in “Methods.” a Principal component analysis (PCA) of R&Zflox and R&Zdel. Each data point represents one sample. Note that PC1 is strongly correlated with gender, whereas PC3 separates R&Zflox mice from R&Zdel mice. PC2 corresponded to the two batches (batch1 and batch 2) from which the data were generated. b Graphs showing top 3 gene ontology (GO) terms significantly enriched for genes upregulated (red) and downregulated (purple) in R&Zdel compared to R&Zflox. Full list in Supplementary Data 1. c Venn diagram showing a correlation between genes involved in lipid metabolism (brown), TCF4 target genes (green) and genes DE at any time point in R&Zdel livers (purple). The numbers denote the number of genes in each comparison. Details are given in Supplementary Data 3. d, e Heatmaps of the lipid metabolism genes DE in R&Zdel livers. d Genes DE averaged between all mice per time point and ranked by fold change with respect to their respective R&Zflox control. e DE genes showing some representative lipid metabolic genes. Likelihood ratio test and Benjamini–Hochberg correction; Fasn, 3M *p = 0.0446, 7M ***p = 0.0001; Fads1, 3M ***p = 0.0006; Fads2, 1M ***p = 0.0038, 3M ***p = 0.0001, 7M *p = 0.0282; Elovl2, 3M *p = 0.0392, 7M **p = 0.0088; Elovl6, 3M **p = 0.0020, 7M **p = 0.0088. f Heatmap of the RPKM values (raw z-scored) of DE lipid metabolic genes found to be TCF4 targets. Each column, one independent biological replicate. Source data are provided as a Source data file.
