biostudies-literaturePitter KLNCI NIH HHSNIH HHS3549-3560https://www.ebi.ac.uk/biostudies/studies/S-EPMC9532381biostudies-literatureUnknown82(19)Intratumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including pancreatic ductal adenocarcinoma (PDAC). As PDAC portends a dire prognosis, a better understanding of the mechanisms underpinning cellular diversity in PDAC is crucial. Here, we investigated the cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. Heterogeneity contracted significantly in two-dimensional and three-dimensional cell culture models but was restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquired cell states identified in autochthonous PDAC tumors, including a basal state exhibiting coexpression and coaccessibility of epithelial and mesenchymal genes. Lineage tracing combined Cancer researchSystematic Comparison of Pancreatic Ductal Adenocarcinoma Models Identifies a Conserved Highly Plastic Basal Cell State.PMC9532381T32 CA009207P30 CA008748R37 CA244911DP5 OD031864Wu KPe'er DBhutkar AFerrena ASinghal AHudson ABlum Mde Stanchina ETammela TChaligne RGrbovic-Huezo OJoost SLecomte NIacobuzio-Donahue CAPitter KLHolm MfalseSystematic Comparison of Pancreatic Ductal Adenocarcinoma Models Identifies a Conserved Highly Plastic Basal Cell State.Intratumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including pancreatic ductal adenocarcinoma (PDAC). As PDAC portends a dire prognosis, a better understanding of the mechanisms underpinning cellular diversity in PDAC is crucial. Here, we investigated the cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. Heterogeneity contracted significantly in two-dimensional and three-dimensional cell culture models but was restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquired cell states identified in autochthonous PDAC tumors, including a basal state exhibiting coexpression and coaccessibility of epithelial and mesenchymal genes. Lineage tracing combined 2022-01-01T00:00:00Z2022 Oct2026-05-28T03:54:22.126Z2024-11-21T05:41:55.975ZS-EPMC95323813595236010.1158/0008-5472.CAN-22-174210.1158/0008-5472.can-22-1742