美国波士顿儿童医院Carla F. Kim等研究人员合作利用类器官模型揭示肺上皮祖细胞中致癌性KRAS活化的转录特征。该项研究成果于2020年9月4日在线发表在《细胞—干细胞》杂志上。

Title: Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells

Author: Antonella F.M. Dost, Aaron L. Moye, Marall Vedaie, Linh M. Tran, Eileen Fung, Dar Heinze, Carlos Villacorta-Martin, Jessie Huang, Ryan Hekman, Julian H. Kwan, Benjamin C. Blum, Sharon M. Louie, Samuel P. Rowbotham, Julio Sainz de Aja, Mary E. Piper, Preetida J. Bhetariya, Roderick T. Bronson, Andrew Emili, Gustavo Mostoslavsky, Gregory A. Fishbein, William D. Wallace, Kostyantyn Krysan, Steven M. Dubinett, Jane Yanagawa, Darrell N. Kotton, Carla F. Kim

Issue&Volume: 2020-09-04

Abstract: Mutant KRAS is a common driver in epithelial cancers. Nevertheless, molecular changesoccurring early after activation of oncogenic KRAS in epithelial cells remain poorlyunderstood. We compared transcriptional changes at single-cell resolution after KRASactivation in four sample sets. In addition to patient samples and genetically engineeredmouse models, we developed organoid systems from primary mouse and human induced pluripotentstem cell-derived lung epithelial cells to model early-stage lung adenocarcinoma.In all four settings, alveolar epithelial progenitor (AT2) cells expressing oncogenicKRAS had reduced expression of mature lineage identity genes. These findings demonstratethe 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 organoidtools to study the transcriptional and proteomic changes that distinguish normal epithelialprogenitor cells from early-stage lung cancer, facilitating the search for targetsfor KRAS-driven tumors.

DOI: 10.1016/j.stem.2020.07.022

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(20)30360-X