Extended Data Fig. 7: Analysis of liver and lung metastasis-like chromatin and transcriptional states in murine premalignant pancreas and human PDAC.

(a) UMAP visualization of scATAC-seq profiles of Kras-mutant pancreatic epithelial cells (mKate2+) +/- cerulein injury (n = 1 mouse for each) from ref. 35 (see Methods for details). Signature scores based on liver- or lung-specific ATAC-open peaks from bulk ATAC-seq data are displayed in color per individual cell. (b) Schematic of scRNA-seq experiment in premalignant pancreas. Created in BioRender. Tsanov, K. (2025) https://BioRender.com/52xbslm. (c) (Left) UMAP visualization of scRNA-seq profiles of KC-shRen and KC-shSmad4 ( + Dox) pre-malignant pancreatic tissue (mKate2+) (identical to Fig. 6d). (Middle & Right) Signature scores based on liver- or lung-specific genes corresponding to organ-enriched ATAC-open peaks are displayed in color per individual cell. Data represent 4 independent mice. (d) UMAP visualization of scRNA-seq profiles of human primary PDAC tumor cells from ref. 37 (see Methods for details). Signature scores based on scRNA-seq profiles of mouse liver- or lung-specific ATAC-open cell populations (from the matching scATAC-seq multiomics data) are displayed in color per individual cell. (e) Gastric- and progenitor-like signature scores corresponding to panel (d). (f) Correlation analysis of liver/lung metastasis-like vs. gastric/progenitor-like transcriptional signatures. The size and color of each circle reflects correlation strength. Exact correlation scores are shown for each comparison. Statistical analysis by Pearson correlation.