Transcriptomic profiling of drug-treated human induced pluripotent stem cells (iPSCs) [Conv-GEO-Depot]

Kinase inhibitors (KIs) are a promising alternative to traditional chemotherapeutics in the treatment of multiple cancer types. Unfortunately, some kinase inhibitors induce cardiotoxicity as a severe side effect. To identify gene expression signatures that might be indicative of kinase inhibitor-induced cardiotoxicity, we generated six cardiomyocyte cell lines from induced pluripotent stem cells that we obtained from six healthy volunteers. Treatment of these cell lines with 54 FDA-approved drugs, i.e. 23 kinase inhibitors, 4 monoclonal antibodies, 4 anthracyclines, 7 cardiac acting and 16 non-cardiac acting drugs, allowed generation of 266 lists of differentially expressed genes. We subjected those lists to unsupervised and supervised algorithms to identify differentially expressed pathway activities associated with cardiotoxic responses. Overall design: Six different iPSC-derived cardiomyocyte cell lines were treated with one out of 54 FDA-approaved drugs or DMSP for 48 hours, followed by bulk RNAseq analysis. Differentially expressed genes were identified between drug- and control treated cell lines.