Effect of TOP2B deletion or catalytic inhibition on gene expression in iPSC-derived human cardiomyocytes

DNA topoisomerase IIB (TOP2B) is required for the correct execution of certain developmental transcription programs. Here, we have compared the transcriptional changes accompanying differentiation of wild type and TOP2B null human iPSC cells to beating cardiomyocytes. In addition we assess the transcriptional effect of short term (3hr) application of two TOP2B catalytic inhibitors in iPSC-derived cardiomyocytes. Human iPSC cells were differentiated to produce beating cardiomyocytes. RNA was prepared from undifferentiated iPSC cells and from induced cardiomyocytes once they had formed sheets of beating cells. Cardiomyocytes were untreated (control) or exposed to TOP2 inhibitors dexrazoxane (ICRF-187) or topobexin for 3 hours immediately prior to cell lysis and RNA preparation. For all conditions four replica RNA isolations were performed.