| Literature DB >> 32891189 |
Antonella F M Dost1, Aaron L Moye1, Marall Vedaie2, Linh M Tran3, Eileen Fung4, Dar Heinze5, Carlos Villacorta-Martin6, Jessie Huang2, Ryan Hekman7, Julian H Kwan7, Benjamin C Blum7, Sharon M Louie1, Samuel P Rowbotham1, Julio Sainz de Aja1, Mary E Piper8, Preetida J Bhetariya9, Roderick T Bronson10, Andrew Emili11, Gustavo Mostoslavsky5, Gregory A Fishbein12, William D Wallace13, Kostyantyn Krysan3, Steven M Dubinett14, Jane Yanagawa15, Darrell N Kotton16, Carla F Kim17.
Abstract
Mutant KRAS is a common driver in epithelial cancers. Nevertheless, molecular changes occurring early after activation of oncogenic KRAS in epithelial cells remain poorly understood. We compared transcriptional changes at single-cell resolution after KRAS activation in four sample sets. In addition to patient samples and genetically engineered mouse models, we developed organoid systems from primary mouse and human induced pluripotent stem cell-derived lung epithelial cells to model early-stage lung adenocarcinoma. In all four settings, alveolar epithelial progenitor (AT2) cells expressing oncogenic KRAS had reduced expression of mature lineage identity genes. These findings demonstrate the utility of our in vitro organoid approaches for uncovering the early consequences of oncogenic KRAS expression. This resource provides an extensive collection of datasets and describes organoid tools to study the transcriptional and proteomic changes that distinguish normal epithelial progenitor cells from early-stage lung cancer, facilitating the search for targets for KRAS-driven tumors.Entities:
Keywords: KRAS; alveolar; developmental programs; early-stage lung cancer; iPSC; loss of differentiation; organoid; single-cell RNA sequencing; stage IA lung adenocarcinoma; tumor progression
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Year: 2020 PMID： 32891189 PMCID： PMC7541765 DOI： 10.1016/j.stem.2020.07.022
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633