Fig. 5: Functional and transcriptional subtype heterogeneity in liver metastases.

a For one patient, organoid lines were derived from the primary tumor (P) as well as two liver metastases (M1 and M2). Shown is a UMAP representation of transcriptomes integrated by reciprocal PCA, with shared and organoid line-specific cell clusters identified by unsupervised clustering. Cells are colored by sample origin (left) and cluster membership (right). b Expression of genes involved in cell cycle (MKI67), secretion and digestion (FABP1, PRSS1, and PGC), and immune regulation (CD70, TMEM176B) across cells from P, M1, and M2 organoids. c Expression of the top 10 enriched genes for each cluster. d Moffitt subtype scores from bulk RNA-seq data (left) and single-cell RNA-seq data (right) for P, M1, and M2 organoids. Blue indicates classical subtype scores, red basal-like (“Methods”). Cells are grouped by cluster identity according to (a) in the violin plots. e Projection of M1 and M2 transcriptomes onto the primary PDAC organoid data (see Fig. 4f and “Methods”) shows the distribution of cells across cycling and differentiating clusters.