Fig 2: Early lesions and tumor incidence.A Representative H&E stainings showing 3 and 9 month old pancreata from KC, Gkn1KC and Gkn2KC mice. Lesion occupied area is framed in red (scale bars 200 µm). Right panel shows area quantification of occupying lesions at 3, 6, and 9 months time points (one-way ANOVA). B Time dependent probability of malignant occurrence curve displays all animals presenting malignancy. Mice were sacrificed when termination criteria were met or 9 month’s time point was reached; (Gehan–Breslow–Wilcoxon analysis). Right panel shows % of mice harboring a tumor KC = 21%, Gkn1KC = 44% and Gkn2 = 39%. * including Gkn1 heterozygous-KC.

Fig 3: In vitro and in vivo effects of GKN1 protein.A Viability of Panc-02 cells was assessed by MTT colorimetric assay after 24 h of incubation with conditioned media containing GKN1 protein. B ß-Galactosidase staining on Panc-02 cells after incubation with GKN1 or control conditioned medium. Representative pictures of compared groups are shown for the 72 h time point. Expression profile of senescence genes such as p16 and p21 was performed via qPCR analysis on Panc-02 cells treated with conditioned media with or without GKN1. Gene expression was analyzed over 24, 48, and 72 h. C Migration assay of Panc-02 cells after 24 h of incubation with GKN1 or control conditioned medium. Representative pictures at 5x magnification show migration over 1, 10, and 24 h time period (scale bars 200 µm). D In vitro transdifferentiation of isolated acinar cells from KC mice, treated with conditioned media containing GKN1. E Subcutaneous tumor development over 19 days after injection of either Panc-02-empty vector or Gastrokine1+ Panc-02 cells.

Fig 4: Gastrokine expression in KPC mice.A Gkn1 and Gkn2 transcripts in 4 months old KPC mice compared to age matched wild-type mice. B Visualization of tumor and peri-tumoral tissue in 4 months old KPC mice. H&E, GKN1, and GKN2 immunohistochemistry in consecutive cuts (scale bars 100 µm).

Fig 5: H. pylori target population is characterized by a high level of cell differentiation.a Volcano plot showing log-fold change and -log (p-value) for the comparison between cluster 4 (H. pylori-infected enriched cluster) and the rest of the clusters (clusters 1, 2 and 3). Red dots denote DEG with p-value = 0.05 and =1.5 log2 fold change. Blue dots denote DEG with p-value = 0.05 and =1.5 log2 fold change. b Expression of several DEG shown in panel (a). Expression is colour-coded and projected on the t-SNE as in Fig. 2c. c Protein levels of PSCA, cleaved PARP, phosphorylated H2AX and YAP in 2D naïve monolayers measured by mass spectrometry (CyTOF). Every dot represents an individual cell and colours denote the intensity of the signal. d Confocal microscopic image of human stomach mucosa co-stained for MUC5AC (red), GKN1 (green, upper panel) and GKN2 (green, lower panel) using immunofluorescence. Nuclei were counterstained using Hoechst 33342 (blue). Scale bar: 50 µm. Data in panel c is representative results of organoid lines derived from 3 donors and 1 experiment. Data in panel d is representative of results from 2 donors and 1 experiment.