Fig. 4. Transcriptomic comparison allows prediction of HLC functionality.

a Scatter plot of protein abundance ratios against corresponding mRNA ratios in HepG2 cells vs. PHHs for proteins/genes that are detected in both transcriptome (from our transcriptomic comparison) and proteome (from Tascher et al.⁶⁸). Pearson’s coefficient of determination (R²) is shown at the top left of the plot. b Scatter plot of enriched pathways based on transcriptome and proteome. Only pathways that are enriched on both the transcriptomic and proteomic levels are shown. c Heatmap and DBS of hepatitis B associated genes according to the DisGeNET database. Red highlight indicates the predicted optimal hepatocyte in vitro models. d Correlation plot of the gene expression levels of ALB from the transcriptomic comparison data (x-axis) and the reported relative albumin secretion (y-axis) in included HLCs. Pearson’s coefficient of determination (R²) and P value (p) are shown on the bottom right of the graph (n = 11 biologically independent samples). Dotted lines represent the 95% confidence interval. e CYP3A4 activities presented as mean. f Gene expression level of CYP3A4 from the transcriptomic comparison data presented as mean ± standard deviation. g The DBS of urea cycle genes according to the Reactome database. The combined values of Chol-HLC, fibroblast, HepG2 cell, FHep-HLC, and PHH/liver samples from different studies are presented. h Urea secretion level presented as mean. i Gene expression level of CPS1 and OTC from the transcriptomic comparison data presented as mean ± standard deviation. Box-and-whisker plots are shown as median (line), interquartile range (box), and data range or 1.5x interquartile range (whisker). Source data are provided in Supplementary Data 7.