当前位置: X-MOL 学术Cell Stem Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Organoids Model Transcriptional Hallmarks of Oncogenic KRAS Activation in Lung Epithelial Progenitor Cells.
Cell Stem Cell ( IF 23.9 ) Pub Date : 2020-09-04 , DOI: 10.1016/j.stem.2020.07.022
Antonella F M Dost 1 , Aaron L Moye 1 , Marall Vedaie 2 , Linh M Tran 3 , Eileen Fung 4 , Dar Heinze 5 , Carlos Villacorta-Martin 6 , Jessie Huang 2 , Ryan Hekman 7 , Julian H Kwan 7 , Benjamin C Blum 7 , Sharon M Louie 1 , Samuel P Rowbotham 1 , Julio Sainz de Aja 1 , Mary E Piper 8 , Preetida J Bhetariya 9 , Roderick T Bronson 10 , Andrew Emili 11 , Gustavo Mostoslavsky 5 , Gregory A Fishbein 12 , William D Wallace 13 , Kostyantyn Krysan 3 , Steven M Dubinett 14 , Jane Yanagawa 15 , Darrell N Kotton 2 , Carla F Kim 1
Affiliation  

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.



中文翻译:

类器官模拟肺上皮祖细胞中致癌 KRAS 激活的转录标志。

KRAS 突变是上皮癌的常见驱动因素。然而,上皮细胞中致癌 KRAS 激活后早期发生的分子变化仍然知之甚少。我们在四个样本组中比较了 KRAS 激活后单细胞分辨率的转录变化。除了患者样本和基因工程小鼠模型之外,我们还利用原代小鼠和人诱导多能干细胞衍生的肺上皮细胞开发了类器官系统,以模拟早期肺腺癌。在所有四种情况下,表达致癌 KRAS 的肺泡上皮祖细胞 (AT2) 成熟谱系识别基因的表达均减少。这些发现证明了我们的体外类器官方法在揭示致癌 KRAS 表达的早期后果方面的实用性。该资源提供了广泛的数据集,并描述了类器官工具,用于研究区分正常上皮祖细胞和早期肺癌的转录和蛋白质组变化,从而促进寻找 KRAS 驱动肿瘤的靶点。

更新日期:2020-10-02
down
wechat
bug