Data from: Expression profiling of human pluripotent stem cell-derived cardiomyocytes exposed to doxorubicin—integration and visualization of multi-omics data

Anthracyclines, such as doxorubicin, are highly efficient chemotherapeutic agents against a variety of cancers. However, anthracyclines are also among the most cardiotoxic therapeutic drugs presently on the market. Chemotherapeutic-induced cardiomyopathy is one of the leading causes of disease and mortality in cancer survivors. The exact mechanisms responsible for doxorubicin-induced cardiomyopathy are not completely known, but the fact that the cardiotoxicity is dose-dependent and that there is a variation in time-to-onset of toxicity, and gender- and age differences suggests that several mechanisms may be involved. In this study, we investigated doxorubicin-induced cardiotoxicity in human pluripotent stem cell-derived cardiomyocytes using proteomics. In addition, different sources of omics data (protein, mRNA, and microRNA) from the same experimental setup were further combined and analyzed using newly developed methods to identify differential expression in data of various origin and types. Subsequently, the results were integrated in order to generate a combined visualization of the findings. In our experimental model system, we exposed cardiomyocytes derived from human pluripotent stem cells to doxorubicin for up to 2 days, followed by a wash-out period of additionally 12 days. Besides an effect on the cell morphology and cardiomyocyte functionality, the data show a strong effect of doxorubicin on all molecular levels investigated. Differential expression patterns that show a linkage between the proteome, transcriptome, and the regulatory microRNA network, were identified. These findings help to increase the understanding of the mechanisms behind anthracycline-induced cardiotoxicity and suggest putative biomarkers for this condition.蒽环类药物（Anthracyclines）如多柔比星（doxorubicin），是针对多种癌症的高效化疗药物。然而，蒽环类药物也是目前临床在售的心脏毒性最强的治疗药物之一。化疗相关心肌病是癌症幸存者发病与死亡的主要诱因之一。目前，多柔比星诱导心肌病的确切致病机制尚未完全阐明，但已知其心脏毒性具有剂量依赖性，且毒性发作时间存在个体差异，同时伴随性别与年龄层面的差异，这提示该过程可能涉及多种致病机制。本研究依托蛋白质组学（proteomics）技术，探究了多柔比星诱导人多能干细胞分化心肌细胞产生心脏毒性的过程。此外，本研究还结合同一实验体系下获取的多组学（omics）数据——包括蛋白质组、mRNA及微小RNA（microRNA）数据，依托新开发的分析方法，对不同来源与类型的组学数据中的差异表达情况进行联合分析。随后，本研究对分析结果进行整合，以实现研究发现的可视化联合展示。在本实验模型中，研究人员将人多能干细胞分化而来的心肌细胞暴露于多柔比星环境中长达2天，随后设置了为期12天的洗脱期。实验数据显示，多柔比星不仅会影响细胞形态与心肌细胞功能，还对所有检测的分子层面均产生显著影响。本研究成功鉴定出连接蛋白质组、转录组（transcriptome）与调控性微小RNA网络的差异表达模式。本研究结果有助于加深人们对蒽环类药物诱导心脏毒性致病机制的理解，同时为该病症提出了潜在的生物标志物候选。