Rawla, P., Sunkara, T. & Gaduputi, V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J. Oncol. 10, 10–27 (2019).
Jan, M. et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci. Transl. Med. 4, 149ra118 (2012).
Barker, N. et al. Crypt stem cells as the cells-of-origin of intestinal cancer. Nature 457, 608–611 (2009).
Murtaugh, L. C. & Keefe, M. D. Regeneration and repair of the exocrine pancreas. Annu. Rev. Physiol. 77, 229–249 (2015).
Desai, B. M. et al. Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration. J. Clin. Invest. 117, 971–977 (2007).
Westphalen, C. B. et al. Dclk1 defines quiescent pancreatic progenitors that promote injury-induced regeneration and tumorigenesis. Cell Stem Cell 18, 441–455 (2016).
Sangiorgi, E. & Capecchi, M. R. Bmi1 lineage tracing identifies a self-renewing pancreatic acinar cell subpopulation capable of maintaining pancreatic organ homeostasis. Proc. Natl Acad. Sci. USA 106, 7101–7106 (2009).
Hruban, R. H., Goggins, M., Parsons, J. & Kern, S. E. Progression model for pancreatic cancer. Clin. Cancer Res. 6, 2969–2972 (2000).
Kopp, J. L. et al. Identification of Sox9-dependent acinar-to-ductal reprogramming as the principal mechanism for initiation of pancreatic ductal adenocarcinoma. Cancer Cell 22, 737–750 (2012).
Habbe, N. et al. Spontaneous induction of murine pancreatic intraepithelial neoplasia (mPanIN) by acinar cell targeting of oncogenic Kras in adult mice. Proc. Natl Acad. Sci. USA 105, 18913–18918 (2008).
De La, O. J. et al. Notch and Kras reprogram pancreatic acinar cells to ductal intraepithelial neoplasia. Proc. Natl Acad. Sci. USA 105, 18907–18912 (2008).
Flowers, B. M. et al. Cell of origin influences pancreatic cancer subtype. Cancer Discov. 11, 660–677 (2021).
Boj, S. F. et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160, 324–338 (2015).
Lee, J. et al. Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells. Nat. Commun. 8, 14686 (2017).
Kanda, M. et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 142, 730–733.e739 (2012).
Shi, C. et al. KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with PanIN: implications for the human pancreatic cancer cell of origin. Mol. Cancer Res. 7, 230–236 (2009).
Jones, S. et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 321, 1801–1806 (2008).
Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4, 437–450 (2003).
Ying, H. et al. Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev. 30, 355–385 (2016).
Roake, C. M. & Artandi, S. E. Regulation of human telomerase in homeostasis and disease. Nat. Rev. Mol. Cell Biol. 21, 384–397 (2020).
Pech, M. F. et al. High telomerase is a hallmark of undifferentiated spermatogonia and is required for maintenance of male germline stem cells. Genes Dev. 29, 2420–2434 (2015).
Petersen, G. M. et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat. Genet. 42, 224–228 (2010).
Lin, S. et al. Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury. Nature 556, 244–248 (2018).
Morris, J. P. T., Cano, D. A., Sekine, S., Wang, S. C. & Hebrok, M. Beta-catenin blocks Kras-dependent reprogramming of acini into pancreatic cancer precursor lesions in mice. J. Clin. Invest. 120, 508–520 (2010).
Pylayeva-Gupta, Y., Grabocka, E. & Bar-Sagi, D. RAS oncogenes: weaving a tumorigenic web. Nat. Rev. Cancer 11, 761–774 (2011).
Collins, M. A., Yan, W., Sebolt-Leopold, J. S. & Pasca di Magliano, M. MAPK signaling is required for dedifferentiation of acinar cells and development of pancreatic intraepithelial neoplasia in mice. Gastroenterology 146, 822–834.e827 (2014).
Bryant, K. L., Mancias, J. D., Kimmelman, A. C. & Der, C. J. KRAS: feeding pancreatic cancer proliferation. Trends Biochem. Sci 39, 91–100 (2014).
Martincorena, I. et al. Somatic mutant clones colonize the human esophagus with age. Science 362, 911–917 (2018).
Martincorena, I. et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science 348, 880–886 (2015).
Busque, L. et al. Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis. Nat. Genet. 44, 1179–1181 (2012).
Madisen, L. et al. A robust and high-throughput Cre reporting and characterization system for the whole mouse brain. Nat. Neurosci. 13, 133–140 (2010).
Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243–3248 (2001).
Kopinke, D. et al. Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreas. Dev. Biol. 362, 57–64 (2012).
Hegyi, P. et al. l-arginine-induced experimental pancreatitis. World J. Gastroenterol. 10, 2003–2009 (2004).
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