Extended Data Fig. 11: Identification of PROX1 as a fetal-state associated transcription factor.

a, Gene trends along aligned canonical–non-canonical axes, of the 6 top-ranked fetal-associated human TFs in four patients. TFs are ranked according to their mean correlations of imputed gene expression with the fetal signature score in these patients. b, Relative expression, from scRNA-seq data, of top 6 fetal-associated TFs in OKG146P (light bars) and OKG146Li (dark bars) organoids cultured for 7 d in HISC media containing 250 nM irinotecan, compared to HISC media alone. c, Pearson correlation of PROX1 expression with module gene expression across this cohort or the ref. ²⁸ cohort. Genes are grouped by module and ordered within each module by hierarchical clustering; modules are ordered by average correlation with PROX1 expression. d, Hematoxylin and eosin (H&E) and immunofluorescence imaging of PROX1, CDX2 (intestinal lineage) and VIM (vimentin, stroma), showing PROX1 expression in poorly differentiated cells along the invasion fronts of two patient primary tumors.