Our study reveals that a commonly used non- integrating reprogramming method can subtly but stably alter transcriptional patterns in iPSCs (Fig. 2B,C). However, the transcriptional signature introduced by SeV infection (63 DEGs) did not separate hESCs from hiPSCs previously generated with retroviral or episomal vectors, suggesting that each reprogramming system may introduce unique transcriptional alterations into iPSCs (Supplementary Fig. 4F,I). Whereas the molecular mechanisms of this observation remain to be elucidated, our findings highlight the importance of controlling for the method of iPSC induction when studying transcriptional patterns in iPSCs. Indeed, a recent comparison of hiPSCs generated with different OKSM delivery systems showed that hiPSCs derived with integrating vectors (e.g., retroviral transgenes) more often exhibit expression, methylation and differentiation defects compared to hiPSCs produced with non-integrating approaches39.
