Megan C. Procario

Supplementary Figure S1. Healthy Donor Pancreas (Validation Dataset). Supplementary Figure S2. A. Dot plot showing marker genes for each cell type in scRNAseq data. Supplementary Figure S3. A. UMAP representation of scRNAseq data of PDAC individual samples colored by Numbat joint CNV probability based on gene expression and heterozygous SNPs beta-allele frequency (BAF) ratio. Supplementary Figure S4. A. Hematoxylin and Eosin (H&E) of healthy and PDAC samples profiled with 10x Genomics CytAssist Visium platform, with overlaid Visium spots. Supplementary Figure S5. A. Dot plot showing marker genes for each spatial domain in spatial transcriptomics data. Supplementary Figure S6. A. Heatmap showing pairwise Pearson correlation between different spatial domains in different tissue types annotated by spatial domain information and tissue type. Supplementary Figure S7. A. Heatmap showing scaled expression of leading edge genes from GSEA of OXIDATIVE_PHOSPHORYLATION, FATTY_ACID_METABOLISM and BILE_ACID_METABOLISM. Supplementary Figure S8. A. Heatmap showing scaled expression of leading edge genes from GSEA of TNFA_SIGNALING_VIA_NFKB, EPITHELIAL_MESENCHYMAL_TRANSITION, INTERFERON_ ALPHA_RESPONSE, HYPOXIA, KRAS_SIGANLING_UP and IL6_JAK_STAT3_SIGNALING. Supplementary Figure S9. A. Spatial map showing the distribution of plasma cells and macrophages around neoplastic domains (PanIN, GLTumor and PDTumor) in healthy, adjacent normal and PDAC samples. Supplementary Figure S10. A. Spatial map showing the abundance and distribution of tertiary lymphoid structures around neoplastic domains in healthy, adjacent normal and PDAC tissue samples. Colors represent annotated spatial domains.

Supplementary Figure S11. A. High magnification hematoxylin and eosin (H&E) image with the Visium spots overlaid, showing adjacency of Fibro1 and Adipose domains, colored by the annotated spatial domain. Supplementary Figure S12. A. Spatially-informed clustering results from donor samples validation dataset, showing 9 different spatial domains based on gene expression from all cells in the spot. Supplementary Figure S13. A. Violin plot showing the Fibro2 and Fibro3 signature score in the fibroblast spatial domain of the donor samples validation dataset. Supplementary Figure S14. A. UMAP representation of integrated Xenium samples from Fiorini et al. (81) dataset, colored by annotated cell type. Supplementary Figure S15. A. Dot plot showing the expression of WNT ligands, receptors and downstream targets in different spatial domains from spatial transcriptomics data. Supplementary Figure S16. A. UMAP representation of scRNAseq data from the mono- and co-culture experiment.

Supp Table 1 from Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer

Supp Table 10 from Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer

ScRNAseq Macrophages Subset Markers

ScRNAseq Fibroblasts Subset Markers

Fibro2 and Fibro3 Genesets for Xenium Projection

Supp Table 14 from Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer

Supp Table 2 from Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer

Supp Table 3A from Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer