journal contribution
posted on 2023-03-31, 05:41 authored by Kenneth L. Pitter, Olivera Grbovic-Huezo, Simon Joost, Anupriya Singhal, Melissa Blum, Katherine Wu, Matilda Holm, Alexander Ferrena, Arjun Bhutkar, Anna Hudson, Nicolas Lecomte, Elisa de Stanchina, Ronan Chaligne, Christine A. Iacobuzio-Donahue, Dana Pe'er, Tuomas Tammela Supplementary Data from Systematic Comparison of Pancreatic Ductal Adenocarcinoma Models Identifies a Conserved Highly Plastic Basal Cell State
Funding
National Cancer Institute (NCI)
United States Department of Health and Human Services
Find out more...NIH Office of the Director (OD)
Cycle for Survival
Rita Allen Foundation (RAF)
American Cancer Society (ACS)
V Foundation for Cancer Research (VFCR)
Hope Funds for Cancer Research (HFCR)
History
ARTICLE ABSTRACT
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 with single-cell transcriptomics revealed that basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intratumoral heterogeneity in PDAC.
This work provides important insights into how different model systems of pancreatic ductal adenocarcinoma mold the phenotypic space of cancer cells, highlighting the power of in vivo models.
