{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T19:18:00Z","timestamp":1783106280367,"version":"3.54.6"},"reference-count":100,"publisher":"Elsevier BV","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2027,6,10]],"date-time":"2027-06-10T00:00:00Z","timestamp":1812585600000},"content-version":"am","delay-in-days":374,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100017050","name":"Cycle for Survival","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009859","name":"Memorial Sloan-Kettering Cancer Center Geoffrey Beene Cancer Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009859","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Developmental Cell"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.devcel.2026.04.012","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:40:06Z","timestamp":1779201606000},"page":"1190-1207.e12","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation"],"prefix":"10.1016","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9230-4593","authenticated-orcid":false,"given":"Xian","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyein S.","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dapeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Dixon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renhe","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denis","family":"Torre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Umeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokce","family":"Askan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslihan","family":"Yavas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeyaram Ravichandran","family":"Damodaran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W.","family":"Rickert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajya","family":"Kappagantula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong Cheng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria G.","family":"Aveson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrien","family":"Grimont","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William B.","family":"Fall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Pulecio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J.","family":"Kaplan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianlu Laura","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jen Jen","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven D.","family":"Leach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A.","family":"Iacobuzio-Donahue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Chandwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina S.","family":"Leslie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1145-6199","authenticated-orcid":false,"given":"Danwei","family":"Huangfu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.devcel.2026.04.012_bib1","unstructured":"National Cancer Institute (2023). Cancer Stat Facts: Pancreas Cancer. https:\/\/seer.cancer.gov\/statfacts\/html\/pancreas.html."},{"key":"10.1016\/j.devcel.2026.04.012_bib2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1097\/MPA.0000000000000368","article-title":"Early detection of sporadic pancreatic cancer: summative review","volume":"44","author":"Chari","year":"2015","journal-title":"Pancreas"},{"key":"10.1016\/j.devcel.2026.04.012_bib3","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1097\/01.pas.0000126675.59108.80","article-title":"An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms","volume":"28","author":"Hruban","year":"2004","journal-title":"Am. J. Surg. Pathol."},{"key":"10.1016\/j.devcel.2026.04.012_bib4","first-page":"2969","article-title":"Progression model for pancreatic cancer","volume":"6","author":"Hruban","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib5","first-page":"2002","article-title":"Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression","volume":"60","author":"Wilentz","year":"2000","journal-title":"Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib6","first-page":"4740","article-title":"Inactivation of the p16 (INK4A) tumor-suppressor gene in pancreatic duct lesions: loss of intranuclear expression","volume":"58","author":"Wilentz","year":"1998","journal-title":"Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib7","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1097\/01.MP.0000086072.56290.FB","article-title":"Multicomponent analysis of the pancreatic adenocarcinoma progression model using a pancreatic intraepithelial neoplasia tissue microarray","volume":"16","author":"Maitra","year":"2003","journal-title":"Mod. Pathol."},{"key":"10.1016\/j.devcel.2026.04.012_bib8","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu, and Cancer Genome Atlas Research Network. (2017). Integrated genomic characterization of pancreatic ductal adenocarcinoma. Cancer Cell 32, 185\u2013203.e13. https:\/\/doi.org\/10.1016\/j.ccell.2017.07.007.","DOI":"10.1016\/j.ccell.2017.07.007"},{"key":"10.1016\/j.devcel.2026.04.012_bib9","doi-asserted-by":"crossref","first-page":"6339","DOI":"10.1158\/1078-0432.CCR-12-1215","article-title":"Clinical significance of the genetic landscape of pancreatic cancer and implications for identification of potential long-term survivors","volume":"18","author":"Yachida","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib10","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1200\/JCO.2008.17.7188","article-title":"DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer","volume":"27","author":"Iacobuzio-Donahue","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.devcel.2026.04.012_bib11","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.3748\/wjg.v9.i12.2764","article-title":"Loss of DPC4 expression and its correlation with clinicopathological parameters in pancreatic carcinoma","volume":"9","author":"Hua","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"10.1016\/j.devcel.2026.04.012_bib12","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","article-title":"Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse","volume":"4","author":"Hingorani","year":"2003","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib13","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.molonc.2013.02.002","article-title":"Genetically engineered mouse models of pancreatic adenocarcinoma","volume":"7","author":"Guerra","year":"2013","journal-title":"Mol. Oncol."},{"key":"10.1016\/j.devcel.2026.04.012_bib14","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1053\/j.gastro.2012.03.002","article-title":"What we have learned about pancreatic cancer from mouse models","volume":"142","author":"P\u00e9rez-Mancera","year":"2012","journal-title":"Gastroenterology"},{"key":"10.1016\/j.devcel.2026.04.012_bib15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.ccr.2005.04.023","article-title":"Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice","volume":"7","author":"Hingorani","year":"2005","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib16","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.ccr.2007.01.012","article-title":"Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice","volume":"11","author":"Guerra","year":"2007","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib17","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/s41586-020-03147-x","article-title":"A gene-environment-induced epigenetic program initiates tumorigenesis","volume":"590","author":"Alonso-Curbelo","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.devcel.2026.04.012_bib18","doi-asserted-by":"crossref","first-page":"2959","DOI":"10.1016\/j.devcel.2023.11.008","article-title":"A reversible epigenetic memory of inflammatory injury controls lineage plasticity and tumor initiation in the mouse pancreas","volume":"58","author":"Falvo","year":"2023","journal-title":"Dev. Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib19","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s43018-020-00134-z","article-title":"Mutant Kras co-opts a proto-oncogenic enhancer network in inflammation-induced metaplastic progenitor cells to initiate pancreatic cancer","volume":"2","author":"Li","year":"2021","journal-title":"Nat. Cancer"},{"key":"10.1016\/j.devcel.2026.04.012_bib100","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2026.03.032","article-title":"Oncogenic and tumor-suppressive forces converge on a progenitor niche at the benign-to-malignant transition","author":"Reyes","year":"2026","journal-title":"Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib20","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/ajg.2017.218","article-title":"Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis","volume":"112","author":"Kirkeg\u00e5rd","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"10.1016\/j.devcel.2026.04.012_bib21","doi-asserted-by":"crossref","DOI":"10.3390\/ijms20030676","article-title":"Inflammation and Pancreatic Cancer: Focus on Metabolism, Cytokines, and Immunity","volume":"20","author":"Padoan","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.devcel.2026.04.012_bib22","doi-asserted-by":"crossref","first-page":"4452","DOI":"10.1242\/dev.096628","article-title":"Artificial three-dimensional niches deconstruct pancreas development in vitro","volume":"140","author":"Greggio","year":"2013","journal-title":"Development"},{"key":"10.1016\/j.devcel.2026.04.012_bib23","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.cell.2014.12.021","article-title":"Organoid models of human and mouse ductal pancreatic cancer","volume":"160","author":"Boj","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib24","article-title":"Human pancreatic beta-like cells converted from fibroblasts","volume":"7","author":"Zhu","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib25","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1016\/j.stemcr.2017.05.019","article-title":"Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells","volume":"8","author":"Trott","year":"2017","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.devcel.2026.04.012_bib26","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.stem.2021.03.005","article-title":"Modeling plasticity and dysplasia of pancreatic ductal organoids derived from human pluripotent stem cells","volume":"28","author":"Breunig","year":"2021","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib27","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.stem.2021.03.022","article-title":"Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids","volume":"28","author":"Huang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib28","doi-asserted-by":"crossref","first-page":"5947","DOI":"10.1073\/pnas.0601273103","article-title":"Both p16(Ink4a) and the p19(Arf)-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse","volume":"103","author":"Bardeesy","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.devcel.2026.04.012_bib29","doi-asserted-by":"crossref","first-page":"26580","DOI":"10.1073\/pnas.1911273116","article-title":"Pancreatic cancer organoids recapitulate disease and allow personalized drug screening","volume":"116","author":"Driehuis","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.devcel.2026.04.012_bib30","doi-asserted-by":"crossref","first-page":"S61","DOI":"10.1038\/modpathol.3800685","article-title":"Pancreatic adenocarcinoma: update on the surgical pathology of carcinomas of ductal origin and PanINs","volume":"20","author":"Hruban","year":"2007","journal-title":"Mod. Pathol."},{"key":"10.1016\/j.devcel.2026.04.012_bib31","doi-asserted-by":"crossref","first-page":"694","DOI":"10.5966\/sctm.2015-0017","article-title":"Tumor-Free Transplantation of Patient-Derived Induced Pluripotent Stem Cell Progeny for Customized Islet Regeneration","volume":"5","author":"El Khatib","year":"2016","journal-title":"Stem Cells Transl. Med."},{"key":"10.1016\/j.devcel.2026.04.012_bib32","doi-asserted-by":"crossref","DOI":"10.3389\/ti.2022.10575","article-title":"Strategies to Improve the Safety of iPSC-Derived beta Cells for beta Cell Replacement in Diabetes","volume":"35","author":"Pellegrini","year":"2022","journal-title":"Transpl. Int."},{"key":"10.1016\/j.devcel.2026.04.012_bib33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature16965","article-title":"Genomic analyses identify molecular subtypes of pancreatic cancer","volume":"531","author":"Bailey","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.devcel.2026.04.012_bib34","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1158\/0008-5472.CAN-04-1413","article-title":"Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells","volume":"65","author":"Prasad","year":"2005","journal-title":"Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib35","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.devcel.2026.04.012_bib36","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-023-40893-8","article-title":"Deciphering early human pancreas development at the single-cell level","volume":"14","author":"Ma","year":"2023","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib37","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18207-z","article-title":"Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells' heterogeneity","volume":"11","author":"Schlesinger","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib38","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1053\/j.gastro.2024.04.031","article-title":"Resolution of Acinar Dedifferentiation Regulates Tissue Remodeling in Pancreatic Injury and Cancer Initiation","volume":"167","author":"Baldan","year":"2024","journal-title":"Gastroenterology"},{"key":"10.1016\/j.devcel.2026.04.012_bib39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1089\/bio.2015.0032","article-title":"A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project","volume":"13","author":"Carithers","year":"2015","journal-title":"Biopreserv. Biobank."},{"key":"10.1016\/j.devcel.2026.04.012_bib40","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-021-02533-6","article-title":"recount3: summaries and queries for large-scale RNA-seq expression and splicing","volume":"22","author":"Wilks","year":"2021","journal-title":"Genome Biol."},{"key":"10.1016\/j.devcel.2026.04.012_bib41","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/ng.3398","article-title":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","volume":"47","author":"Moffitt","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.devcel.2026.04.012_bib42","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nm.2344","article-title":"Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy","volume":"17","author":"Collisson","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.devcel.2026.04.012_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12517-7","article-title":"De novo compartment deconvolution and weight estimation of tumor samples using DECODER","volume":"10","author":"Peng","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib44","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1158\/1078-0432.CCR-19-1467","article-title":"Purity Independent Subtyping of Tumors (PurIST), A Clinically Robust, Single-sample Classifier for Tumor Subtyping in Pancreatic Cancer","volume":"26","author":"Rashid","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib45","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.celrep.2019.06.034","article-title":"FOXA2 Is Required for Enhancer Priming during Pancreatic Differentiation","volume":"28","author":"Lee","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.devcel.2026.04.012_bib46","first-page":"157","article-title":"Loss of ONECUT1 expression in human pancreatic cancer cells","volume":"19","author":"Jiang","year":"2008","journal-title":"Oncol. Rep."},{"key":"10.1016\/j.devcel.2026.04.012_bib47","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/labinvest.2014.47","article-title":"Loss of HNF6 expression correlates with human pancreatic cancer progression","volume":"94","author":"Pekala","year":"2014","journal-title":"Lab. Invest."},{"key":"10.1016\/j.devcel.2026.04.012_bib48","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-021-23237-2","article-title":"Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility","volume":"12","author":"Dhara","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib49","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms14294","article-title":"An integrative approach unveils FOSL1 as an oncogene vulnerability in KRAS-driven lung and pancreatic cancer","volume":"8","author":"Vallejo","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib50","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1016\/j.devcel.2024.07.021","article-title":"FRA1 controls acinar cell plasticity during murine Kras(G12D)-induced pancreatic acinar to ductal metaplasia","volume":"59","author":"Li","year":"2024","journal-title":"Dev. Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib51","doi-asserted-by":"crossref","DOI":"10.1038\/s41421-021-00366-y","article-title":"Integrated single-cell multiomics analysis reveals novel candidate markers for prognosis in human pancreatic ductal adenocarcinoma","volume":"8","author":"Fan","year":"2022","journal-title":"Cell Discov."},{"key":"10.1016\/j.devcel.2026.04.012_bib52","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1126\/science.1170116","article-title":"Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1","volume":"324","author":"Tahiliani","year":"2009","journal-title":"Science"},{"key":"10.1016\/j.devcel.2026.04.012_bib53","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.25384","article-title":"MeCP2 regulates Tet1-catalyzed demethylation, CTCF binding, and learning-dependent alternative splicing of the BDNF gene in Turtle","volume":"6","author":"Zheng","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.devcel.2026.04.012_bib54","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-11905-3","article-title":"EGR1 recruits TET1 to shape the brain methylome during development and upon neuronal activity","volume":"10","author":"Sun","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib55","doi-asserted-by":"crossref","DOI":"10.1126\/science.abd0875","article-title":"QSER1 protects DNA methylation valleys from de novo methylation","volume":"372","author":"Dixon","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.devcel.2026.04.012_bib56","article-title":"TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib57","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41422-019-0195-y","article-title":"Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma","volume":"29","author":"Peng","year":"2019","journal-title":"Cell Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib58","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrg3080","article-title":"Uncovering the role of 5-hydroxymethylcytosine in the epigenome","volume":"13","author":"Branco","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.devcel.2026.04.012_bib59","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/jb\/mvs003","article-title":"Hydroxylation mediates chromatin demethylation","volume":"151","author":"Tsukada","year":"2012","journal-title":"J. Biochem."},{"key":"10.1016\/j.devcel.2026.04.012_bib60","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1053\/j.gastro.2021.04.044","article-title":"TET2 Drives 5hmc Marking of GATA6 and Epigenetically Defines Pancreatic Ductal Adenocarcinoma Transcriptional Subtypes","volume":"161","author":"Eyres","year":"2021","journal-title":"Gastroenterology"},{"key":"10.1016\/j.devcel.2026.04.012_bib61","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1158\/2159-8290.CD-11-0347","article-title":"A central role for RAF\u2192MEK\u2192ERK signaling in the genesis of pancreatic ductal adenocarcinoma","volume":"2","author":"Collisson","year":"2012","journal-title":"Cancer Discov."},{"key":"10.1016\/j.devcel.2026.04.012_bib62","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1158\/2159-8290.CD-10-0044","article-title":"C-Raf is required for the initiation of lung cancer by K-Ras(G12D)","volume":"1","author":"Karreth","year":"2011","journal-title":"Cancer Discov."},{"key":"10.1016\/j.devcel.2026.04.012_bib63","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1158\/1535-7163.MCT-19-0183","article-title":"ERK Inhibitor LY3214996 Targets ERK Pathway-Driven Cancers: A Therapeutic Approach Toward Precision Medicine","volume":"19","author":"Bhagwat","year":"2020","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.devcel.2026.04.012_bib64","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/ng0994-27","article-title":"Frequent somatic mutations and homozygous deletions of the p16 (MTS1) gene in pancreatic adenocarcinoma","volume":"8","author":"Caldas","year":"1994","journal-title":"Nat. Genet."},{"key":"10.1016\/j.devcel.2026.04.012_bib65","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ccr.2009.02.022","article-title":"Oncogenic Braf induces melanocyte senescence and melanoma in mice","volume":"15","author":"Dhomen","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib66","doi-asserted-by":"crossref","DOI":"10.1126\/science.abc1048","article-title":"Developmental chromatin programs determine oncogenic competence in melanoma","volume":"373","author":"Baggiolini","year":"2021","journal-title":"Science"},{"key":"10.1016\/j.devcel.2026.04.012_bib67","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.ccr.2014.03.014","article-title":"Oncogenic Kras activates a hematopoietic-to-epithelial IL-17 signaling axis in preinvasive pancreatic neoplasia","volume":"25","author":"McAllister","year":"2014","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib68","doi-asserted-by":"crossref","DOI":"10.1126\/science.add5327","article-title":"Epigenetic plasticity cooperates with cell-cell interactions to direct pancreatic tumorigenesis","volume":"380","author":"Burdziak","year":"2023","journal-title":"Science"},{"key":"10.1016\/j.devcel.2026.04.012_bib69","article-title":"Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells","volume":"8","author":"Lee","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib70","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1016\/j.stem.2017.12.009","article-title":"Human Pancreatic Tumor Organoids Reveal Loss of Stem Cell Niche Factor Dependence during Disease Progression","volume":"22","author":"Seino","year":"2018","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib71","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1038\/s41551-021-00757-2","article-title":"Single-cell-resolved differentiation of human induced pluripotent stem cells into pancreatic duct-like organoids on a microwell chip","volume":"5","author":"Wiedenmann","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.devcel.2026.04.012_bib72","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.trecan.2022.03.003","article-title":"State-matched organoid models to fight pancreatic cancer","volume":"8","author":"Melzer","year":"2022","journal-title":"Trends Cancer"},{"key":"10.1016\/j.devcel.2026.04.012_bib73","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/path.6156","article-title":"DNA methylation-associated allelic inactivation regulates Keratin 19 gene expression during pancreatic development and carcinogenesis","volume":"261","author":"Kr\u00fcger","year":"2023","journal-title":"J. Pathol."},{"key":"10.1016\/j.devcel.2026.04.012_bib74","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.7150\/thno.78323","article-title":"Single-cell profiling of GP2-enriched pancreatic progenitors to simultaneously create acinar, ductal, and endocrine organoids","volume":"13","author":"Merz","year":"2023","journal-title":"Theranostics"},{"key":"10.1016\/j.devcel.2026.04.012_bib75","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.aah4199","article-title":"Rb1 and Trp53 cooperate to suppress prostate cancer lineage plasticity, metastasis, and antiandrogen resistance","volume":"355","author":"Ku","year":"2017","journal-title":"Science"},{"key":"10.1016\/j.devcel.2026.04.012_bib76","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.ccell.2018.02.003","article-title":"Loss of KDM6A Activates Super-Enhancers to Induce Gender-Specific Squamous-like Pancreatic Cancer and Confers Sensitivity to BET Inhibitors","volume":"33","author":"Andricovich","year":"2018","journal-title":"Cancer Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib77","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1158\/0008-5472.CAN-22-4052","article-title":"Comprehensive DNA Methylation Analysis Indicates That Pancreatic Intraepithelial Neoplasia Lesions Are Acinar-Derived and Epigenetically Primed for Carcinogenesis","volume":"83","author":"Lo","year":"2023","journal-title":"Cancer Res."},{"key":"10.1016\/j.devcel.2026.04.012_bib78","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0128814","article-title":"Pancreatic cancer patient survival correlates with DNA methylation of pancreas development genes","volume":"10","author":"Thompson","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.devcel.2026.04.012_bib79","doi-asserted-by":"crossref","first-page":"2669","DOI":"10.1101\/gad.291021.116","article-title":"PDX1 dynamically regulates pancreatic ductal adenocarcinoma initiation and maintenance","volume":"30","author":"Roy","year":"2016","journal-title":"Genes Dev."},{"key":"10.1016\/j.devcel.2026.04.012_bib80","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1136\/gutjnl-2012-304381","article-title":"Nr5a2 heterozygosity sensitises to, and cooperates with, inflammation in KRas(G12V)-driven pancreatic tumourigenesis","volume":"63","author":"Flandez","year":"2014","journal-title":"Gut"},{"key":"10.1016\/j.devcel.2026.04.012_bib81","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1182\/blood.V72.2.567.567","article-title":"Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia","volume":"72","author":"Huang","year":"1988","journal-title":"Blood"},{"key":"10.1016\/j.devcel.2026.04.012_bib82","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.stem.2016.03.015","article-title":"Genome Editing of Lineage Determinants in Human Pluripotent Stem Cells Reveals Mechanisms of Pancreatic Development and Diabetes","volume":"18","author":"Zhu","year":"2016","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib83","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.stem.2016.01.022","article-title":"CRISPR Interference Efficiently Induces Specific and Reversible Gene Silencing in Human iPSCs","volume":"18","author":"Mandegar","year":"2016","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib84","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.stem.2014.05.018","article-title":"An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells","volume":"15","author":"Gonz\u00e1lez","year":"2014","journal-title":"Cell Stem Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib85","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/nmeth.3047","article-title":"Improved vectors and genome-wide libraries for CRISPR screening","volume":"11","author":"Sanjana","year":"2014","journal-title":"Nat. Methods"},{"key":"10.1016\/j.devcel.2026.04.012_bib86","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nature14136","article-title":"Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex","volume":"517","author":"Konermann","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.devcel.2026.04.012_bib87","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.devcel.2026.04.012_bib88","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"},{"key":"10.1016\/j.devcel.2026.04.012_bib89","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.devcel.2026.04.012_bib90","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1083\/jcb.201202108","article-title":"K-Ras and B-Raf oncogenes inhibit colon epithelial polarity establishment through up-regulation of c-myc","volume":"198","author":"Magudia","year":"2012","journal-title":"J. Cell Biol."},{"key":"10.1016\/j.devcel.2026.04.012_bib91","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1016\/j.celrep.2016.08.048","article-title":"Mammary-Stem-Cell-Based Somatic Mouse Models Reveal Breast Cancer Drivers Causing Cell Fate Dysregulation","volume":"16","author":"Zhang","year":"2016","journal-title":"Cell Rep."},{"key":"10.1016\/j.devcel.2026.04.012_bib92","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41587-020-0430-6","article-title":"Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells","volume":"38","author":"Hogrebe","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.devcel.2026.04.012_bib93","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/B978-0-12-801185-0.00011-8","article-title":"The iCRISPR platform for rapid genome editing in human pluripotent stem cells","volume":"546","author":"Zhu","year":"2014","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.devcel.2026.04.012_bib94","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"10.1016\/j.devcel.2026.04.012_bib95","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1093\/bioinformatics\/btr167","article-title":"Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications","volume":"27","author":"Krueger","year":"2011","journal-title":"Bioinformatics"},{"key":"10.1016\/j.devcel.2026.04.012_bib96","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms7921","article-title":"Epigenomic evolution in diffuse large B-cell lymphomas","volume":"6","author":"Pan","year":"2015","journal-title":"Nat. Commun."},{"key":"10.1016\/j.devcel.2026.04.012_bib97","doi-asserted-by":"crossref","DOI":"10.1007\/s11605-018-3673-5","article-title":"Response to: \"The Role of Bundle Size for Preventing Surgical Site Infections after Colorectal Surgery: Is More Better?\"","volume":"22","author":"Lau","year":"2018","journal-title":"J. Gastrointest. Surg."},{"key":"10.1016\/j.devcel.2026.04.012_bib98","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1038\/s41556-022-00946-4","article-title":"CRISPR screening uncovers a central requirement for HHEX in pancreatic lineage commitment and plasticity restriction","volume":"24","author":"Yang","year":"2022","journal-title":"Nat. Cell Biol."},{"key":"10.1016\/j.devcel.2026.04.012_bib99","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.21856","article-title":"An efficient targeted nuclease strategy for high-resolution mapping of DNA binding sites","volume":"6","author":"Skene","year":"2017","journal-title":"eLife"}],"container-title":["Developmental Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1534580726001590?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1534580726001590?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T18:40:08Z","timestamp":1783104008000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1534580726001590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":100,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["S1534580726001590"],"URL":"https:\/\/doi.org\/10.1016\/j.devcel.2026.04.012","relation":{},"ISSN":["1534-5807"],"issn-type":[{"value":"1534-5807","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Human pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation","name":"articletitle","label":"Article Title"},{"value":"Developmental Cell","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.devcel.2026.04.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}