Figure 2. Wnt signals activate a fibrogenic gene expression program in liver progenitors.

A. Gene networks applying Ingenuity pathway analysis on the 358 gene set differentially regulated by Wnt3a. B. Wnt-induced differentiation of hepatic progenitors into fibrogenic myofibroblast-like cells matches the transcriptome signature of spontaneously emerging EMT in human HCC (GSE26391). 3P and 3SP human HCC cell lines derive from the same tumor, mesenchymal 3SP resulting from epithelial 3P cells that underwent spontaneous EMT in a human HCC [23]. By gene set enrichment analysis, 3SP cells are significantly enriched in transcripts induced by Wnt3a in HepaRG cells. C. and D. Hierarchical clustering: 3SP and 3P cells are distinguished by C Wnt target genes from the Wnt Homepage (Supplementary Table 6A) and D Extracellular Wnt signaling (Wnt pathway ligands and receptors). Raw gene expression data were normalized by the Robust Multi-array Average (RMA) log₂ algorithm and quantile filtered.