Genetic heterogeneity of Induced Pluripotent Stem Cell clones revealed by whole genome sequencing

To comprehensively assess the genetic consequences of induced Pluripotent Stem Cell (iPSC) reprogramming, we performed whole genome sequencing on ten murine iPSC clones derived from three completely independent reprogramming experiments. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 common genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool; these cells were more likely to undergo reprogramming, for reasons that are not yet clear. This data suggests that most of the genetic variation in iPSC clones is not caused by reprogramming per se; it is rather a consequence of cloning individual cells, which "captures" the mutational history of the reprogrammed cell.