KRAS and pancreatic ductal adenocarcinoma: Consistent with the idea that both senescence and tumorigenesis require a high level of oncogenic RAS11,12, spontaneous upregulation of Kras level was detected with disease stage, in which the OIS cluster exhibited higher expression than both their non-senescent pancreatic intraepithelial neoplasia counterparts and the more advanced pancreatic ductal adenocarcinoma stage (Extended Data Fig. 2c–e).