Fig. 2

Early-life HFD-induced changes in hepatocyte gene expression are largely reversed by subsequent NC. A A schematic of tdo2:GFP transgenic medaka construction using CRISPR-Cas9-mediated gene knockin and sorting of GFP-positive hepatocytes. Scale bar: 100 µm B RNA-seq results showing differentially expressed genes in hepatocytes of HFD fish compared to NC. X-axis: log2 fold change (HFD/NC) of expression values, y-axis: –log10 p-value. C Gene ontology analyses of upregulated (upper) and downregulated (lower) genes by HFD for biological processes using PANTHER 17.0. Fold enrichment (orange) and –log10 FDR (bar) are displayed. D Heatmaps of genes belonging to the GO term “lipid metabolic process” (upper) and “translation” (lower) at seven weeks of age. Log2-transformed, and Z-transformed, DESeq2 normalized read counts are displayed. E Differentially expressed genes in hepatocytes of HFD-NC fish compared to NC-NC. F Venn diagram of differentially expressed genes at seven and 15 weeks of age. G A heatmap of differentially expressed genes at seven weeks of age. Log2-transformed, and Z-transformed, DESeq2 normalized read counts are displayed