Gene expression profile at single cell level of Drug-tolerant persister cells induced by targeted therapy in lung adenocarcinoma.

Drug-tolerant persister (DTP) stage is viewed as a major source of non-genetic drug resistance. We use single cell RNA seq to reveal the transcriptomic heterogeniety of DTP stage PC9 cells were treated with 150nM Osimertinib for 4 days or 11 days to induce DTP stage. NCI-H358 cells were treated with 500nM Sotorasib for 8 days to induce DTP stage. All DTP cells (3 samples) and untreated control cells (2 samples) were collected, undergo cell hashing with barcoded antibodies and subsequently pooled in one sc-RNA seq run.

药物耐受持久细胞（Drug-tolerant persister, DTP）阶段被认为是非遗传性药物耐药的主要来源。本研究通过单细胞RNA测序（single cell RNA sequencing, scRNA-seq）解析经诱导的DTP阶段细胞的转录组异质性：将PC9细胞分别以150nM奥希替尼处理4天或11天以诱导DTP阶段；将NCI-H358细胞以500nM索托拉西布处理8天以诱导DTP阶段。随后收集所有DTP细胞（共3份样本）及未处理的对照细胞（共2份样本），采用条形码抗体进行细胞哈希（cell hashing）标记，之后将样本混合并进行单次scRNA-seq测序。