Modeling Braf-induced thyroid cancer development and cell redifferentiation using pluripotent stem cell-derived organoids

To generate a papillary thyroid carcinoma organoid model by inducing the BrafV637E mutation in mouse embryonic stem cells derived functional thyroid follicles to better comprehend the oncogenic events driven by Braf-oncogene and develop a drug screening tool. We performed gene expression profiling analysis using data obtained from bulk RNA-seq of organoid model with and without induction of BrafV637E expression induction, after MEK and PI3K inhibitors addition). Overall design: Comparative gene expression profiling analysis of bulk RNA-seq data of organoids developped from G4 RosaLuc TRE-Nkx2-1-Pax8_bTg-NES-BrafV637E-ERT2 mouse embryonic stem cells with addition of Br-cAMP, Br-cAMP+4-Hydroxytamoxifen and Br-cAMP+4-Hydroxytamoxifen+PD0325901+LY204002.

本研究旨在通过在小鼠胚胎干细胞来源的功能性甲状腺滤泡中诱导BrafV637E突变，构建乳头状甲状腺癌（papillary thyroid carcinoma）类器官模型，以更深入解析BRAF癌基因驱动的致癌事件，并开发药物筛选工具。我们针对两类类器官模型的批量RNA测序（bulk RNA-seq）数据开展基因表达谱分析：一类为经BrafV637E表达诱导且添加MEK抑制剂（MEK inhibitor）与PI3K抑制剂（PI3K inhibitor）的模型，另一类为未进行该诱导且添加上述抑制剂的模型。整体设计：对源自G4 RosaLuc TRE-Nkx2-1-Pax8_bTg-NES-BrafV637E-ERT2小鼠胚胎干细胞的类器官进行比较基因表达谱分析，三组处理分别为添加Br-cAMP、Br-cAMP+4-羟基他莫昔芬（4-Hydroxytamoxifen），以及Br-cAMP+4-羟基他莫昔芬+PD0325901+LY204002。