Supplementary Figures S1-S17 from Inactivation of Notch4 Attenuated Pancreatic Tumorigenesis in Mice

Supplementary Figure 1. Inactivation of Notch1 had no impact on pancreatic tumorigenesis driven by oncogenic Kras in the context of p16 inactivation.

Supplementary Figure 2. Histological analyses of the pancreatic tissues of the PKC, the N1+/- PKC, and the N1fl/flPKC mice revealed no significant differences.

Supplementary Figure 3. Representative H&E from the PKC, the N1+/- PKC, and the N1fl/flPKC mice at 2 months of age (PanIN, A, C, E) and 5 months of age (PDAC, B, D, F).

Supplementary Figure 4. Comparative histological analyses of PanIN lesions in the PKC, the N1+/- PKC, and the N1fl/flPKC mice revealed no significant differences.

Supplementary Figure 5. Inactivation of Notch4 reduced the formation of high-grade PanIN, although not at a statistically significant level.

Supplementary Figure 6. Representative Notch4-ICD expression in the pancreases of PKC mice

Supplementary Figure 7. The expressions of Notch4 and Endomucin were both detected in the endothelial compartment by IHC.

Supplementary Figure 8. Slight differential Endomucin expression was detected between the KC and the N4-/- KC mice by day 21 post the caerulein treatment.

Supplementary Figure 9. Inactivation of Notch4 was associated with reduced but not significant Endomucin-positive angiogenesis at 2 months of age.

Supplementary Figure 10. Inactivation of Notch4 was associated with significant reduction of Endomucin-positive angiogenesis at 5 months of age.

Supplementary Figure 11. Inactivation of Notch4 attenuated desmoplastic reaction in the pancreases treated by Caerulein.

Supplementary Figure 12. Reduced desmoplasia was observed in N4-/- PKC mice when compared to PKC mice.

Supplementary Figure 13. Inactivation of Notch4 did not alter macrophage infiltration in the pancreases treated by Caerulein.

Supplementary Figure 14. Inactivation of Notch4 did not alter macrophage infiltration in the pancreatic tumors induced by oncogenic Kras.

Supplementary Figure 15. scRNA-Seq analysis revealed Notch4 expression in the endothelial and CK19+ normal and tumor cells in pancreatic tumorigenesis.

Supplementary Figure 16. Increased expression of the NGF gene was observed with Notch4 inactivation, but not with a statistically significant association.

Supplementary Figure 17. Notch4 RNA expression level in Panc 08.13 was the highest among candidate human PDAC cell lines.