Fig. 4: Identification of autocrine and paracrine signals that boost human fetal hepatocyte organoid growth.

a Heatmap displaying gene expression patterns of cytokines, chemokines, and growth factors upon FH organoid growth from tissue. The mean expression of n = 2 donors is visualized as row Z-scores. b Comparison between the temporal mRNA expression profiles of selected cytokines and growth factors upon hepatocyte organoid growth from tissue (black) or single FHs (green). The mean expression of n = 2 donors per dataset is plotted (normalized transcripts). c Experimental strategy to evaluate the effect of cytokines and growth factors on human FH organoid growth. d Representative brightfield images of organoid-derived single FHs at day 0 and the outgrowing organoids challenged with indicated cytokines and growth factors at day 7. Representative of n = 2 challenge experiments. Scale bar = 100 μm. e Quantification of the organoid diameter 7 days post organoid outgrowth from single FHs under the different challenges (n = 40 organoids per condition). Mean ± SD is plotted. EREG: *p = 0.0143; AREG: ***p = 0.0005; NRG1, IL1β, IL6, IL10, IL11: ***p < 0.0001, all versus control, one-way ANOVA with Dunnett’s post hoc test. Source data are provided as a Source data file.