Figure 1(A) Top 2 significantly overrepresented expression patterns for ERS UP and ERS DOWN genes following PHx. Data show changes in expression at 4, 10, 48h and 1 week after PHx (0h) for genes comprised within each model profile of dynamic expression identified by STEM. (B) Functional enrichment analyses were performed using ERS UP (upper panels) or ERS DOWN (lower panels) genes and the ToppGene Suite. KEGG Pathways with Bonferroni-corrected p-value <10-3 were considered and similar terms were merged. (C) Bagplots showing the breadth of transcriptomic changes for the indicated datasets. Genes were positioned based on their basal expression levels in the control conditions and their FC (Log2) in the indicated (patho) physiological context. The dark blue area is the "bag" (50% of the data points around the median, which is indicated by a red cross) while the light blue area delimits the "loop" Red dots are outliers. (D-E) Box plots showing normalized expression in liver (D) and liver-specificity index (E) of LIVER-ID genes, UBQ genes and other genes. Liver-specificity index was calculated as the difference of normalized expression in liver (2 replicates) and mean of normalized expression in control tissues (2 replicates per tissue) using data from BioGPS and is reported as Log2. Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-way ANOVA with Welch's correction and Dunnett's Modified Tukey-Kramer pairwise multiple comparison test was used to assess statistical significance, *P < 0.05. (F) Similar analyses using LIVER-ID genes. Box plots showing Log2 FC ERS/Control in MPH (3 independent experiments) (G) for LIVER-ID genes, UBQ genes and other genes. Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-way ANOVA with Welch's correction and Dunnett's Modified Tukey-Kramer pairwise multiple comparison test was used to assess statistical significance, *P < 0.05. Box plots showing Log2 FC ERS/Control in mouse liver (3 mice per group) (H) for LIVER-ID genes, UBQ genes and other genes. Box plots are composed of a box from the 25th to the 75th percentile with the median as a line and min to max as whiskers. One-way ANOVA with Welch's correction and Dunnett's Modified Tukey-Kramer pairwise multiple comparison test was used to assess statistical significance, *P < 0.05. (I) Enrichment plots from gene set enrichment analyses (GSEA) performed using LIVER-ID genes as the gene set and transcriptomic changes induced by acute ERS in MPH (upper panel) or mouse liver (lower panel) as the ranked gene list. NES and FDR (as in all subsequent GSEA panels) are the normalized enrichment score and the false discovery rate provided by the GSEA software, respectively. Genes repressed by ERS in MPH (3 independent experiments) (J) were ranked based on their Log2 FC ERS/Control and divided into quartiles (increased repression from Q1 to Q4). The fraction of LIVER-ID genes in the 4 quartiles was defined and is displayed relative to that obtained for Q1 arbitrarily set to 1. Chi-square test with BH correction for multiple testing was used to assess statistical significance, *P < 0.05. Genes repressed by ERS in mouse liver (3 mice per group) (K) were ranked based on their Log2 FC ERS/Control and divided into quartiles (increased repression from Q1 to Q4). The fraction of LIVER-ID genes in the 4 quartiles was defined and is displayed relative to that obtained for Q1 arbitrarily set to 1. Chi-square test with BH correction for multiple testing was used to assess statistical significance, *P < 0.05. RT-qPCR analyses of selected ERS UP and LIVER-ID genes monitoring expression changes induced by acute ERS in MPH (3 to 9 independent experiments) (L) The bar graphs show means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05. RT-qPCR analyses of selected ERS UP and LIVER-ID genes monitoring expression changes induced by acute ERS in mouse liver (5 to 7 mice per group) (M). The bar graphs show means ± SD (standard deviations). One-sample t-test with BH correction for multiple testing was used to determine if the mean Log2 FC ERS/Control is statistically different from 0, *P < 0.05. (N) Heatmaps showing normalized expression of ERS UP and ERS DOWN genes from MPH (upper panel) or mouse liver (lower panel) in mouse liver at the indicated stages of development. (O) Average expression of ERS DOWN genes from MPH in single-cells from the hepatobiliary lineage. The hepatoblast-to-hepatocyte and hepatoblast-to-cholangiocyte differentiation paths are indicated with arrows.