Our results may have implications for the use of iPSC technology in disease modeling approaches, where hiPSC lines from healthy individuals are usually compared to hiPSC lines from affected individuals. Because of the apparent influence of genetic background on gene expression patterns in both undifferentiated and differentiated cells, it will be critical to study a sufficient number of hiPSC lines to detect robust phenotypes; this is particularly relevant in complex diseases where the causal mutation(s) are not known. When studying monogenic diseases, it may be necessary to introduce mutations into wild- type hESCs or rescue mutations in patient-derived hiPSCs, as different backgrounds may mask subtle transcriptional differences40.
