Figure 5: Lineage conversion is accompanied by global transcriptional remodelling.

(a) Hierarchical clustering of the gene expression values of the sub-set of genes that were differentially expressed between BAML HEP control and TiPP cells at d14, derived from BAML HEPs+LV-TGIF2 (total 592 genes; P<0.01 and FC >4 or <−4) among all samples analysed. Gene probes are located in rows and samples in columns. Gene expression across rows in the heatmap are coloured according to the z-score, such that the mean expression of each row is set to white colour and expression values higher or lower than the mean are graded towards red or blue, respectively. Rows in the heatmap are ordered according to the FC. (b) Heat map (left) illustrating the relative expression levels of selected hepatic genes involved in metabolic activities in HEP control and TiPP cells. Heat map (right) illustrating the relative expression levels of selected pancreatic progenitor genes in HEP control and TiPP cells. The colours in the heatmap are normalized per row by calculating the z-score for each row. Replicates were summarized as the mean. (c) Panther pathways enrichment analysis of differentially regulated genes in HEP control and TiPP cells at d14 (P<0.05 and FC >2 or <−2). For complete gene ontology annotation lists see Supplementary Data 1. (d) Heat map illustrating the relative expression levels of selected Wnt signaling pathway genes. Genes in bold were selected for confirmation by RT-qPCR. (e) Confirmation of microarray gene expression changes by RT-qPCR analysis. Data were normalized to Sdha and represented as Log2-expression ratio between TiPP d14 cells derived from either BAML HEP or primary HEP and their respective control cells. Values shown are mean±s.e.m. (n=3) *P<0.05.