Senescent fibroblasts in the tumor stroma rewire lung cancer metabolism and plasticity. Senescent fibroblasts in the tumor stroma rewire lung cancer metabolism and plasticity

Our study identified a druggable component of the tumor stroma that fulfills the metabolic requirement of tumor cells to acquire a more aggressive phenotype. Overall design: The p16INK4a+ and p16INK4a- lung fibroblasts and tdTomato+ LUAD cells of KPTI mice were isolated by Fluorescence-activated cell sorting (FACS) according to the presence of eGFP signal and analyzed using scRNAseq. tdTomato+ tumor cells were isolated by FACS after digestion of tumor organoids. KPTI mouse lung sections and human LUAD sections were analyzed by Xenium for spatial transcriptomics data.

本研究鉴定出肿瘤间质（tumor stroma）中的一种成药性组分，该组分可满足肿瘤细胞获取更具侵袭性表型的代谢需求。实验整体设计：依据增强绿色荧光蛋白（eGFP）信号的存在与否，通过荧光激活细胞分选术（Fluorescence-activated cell sorting）分离KPTI小鼠的p16INK4a阳性、p16INK4a阴性肺成纤维细胞与tdTomato阳性肺腺癌（lung adenocarcinoma, LUAD）细胞，并采用单细胞RNA测序（scRNAseq）开展分析。经酶解肿瘤类器官后，借助FACS分离得到tdTomato阳性肿瘤细胞。采用Xenium平台对KPTI小鼠肺组织切片及人类肺腺癌组织切片进行空间转录组数据检测分析。