Fig. 1: Temporal transcriptomic characterization of human fetal hepatocyte organoid growth from tissue.

a Experimental strategy to temporally address the transcriptomic changes associated with FH organoid growth from tissue. b Representative brightfield images of FH organoids outgrowing from tissue at day 7 post seeding (left) and an established organoid line. Scale bar = 300 μm. c Representative images of immunofluorescence staining for AFP, ALB, CK7 and CK19 in FH organoids. Scale bar = 150 μm. d Representative image of immunofluorescence staining for Ki-67 and F-actin (left) and MRP2 (right) in FH organoids. Asterisks indicate binucleated hepatocytes. Scale bar = 50 μm. e PCA plot visualizing the temporal transcriptomic changes underlying FH organoid growth from tissue across n = 2 donors. f Heatmap displaying the temporal expression patterns of genes significantly differently expressed at least at one time point versus 0 h (|log2FC| > 0.5, p-adj < 0.05) based on responses of n = 2 donors. The expression patterns are visualized as row Z-scores. The n indicates the number of genes belonging to each cluster. g Temporal Z-score expression of the genes identified in the different fetal tissue gene clusters across n = 2 donors. Mean ± SD is plotted, clusters 1–7: n = 3086, 2509, 3083, 4260, 2872, 2111, and 2330 genes, respectively. h Biological processes/cell types associated with the different temporal gene clusters, based on GO-term enrichment analysis and manual inspection. b–d Representative of characterization of n = 4 expanding FH organoid cultures. Source data are provided as a Source data file.