Cell Stem Cell
Volume 10, Issue 5, 4 May 2012, Pages 570-582
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Article
Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells

https://doi.org/10.1016/j.stem.2012.03.002Get rights and content
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Summary

To assess the genetic consequences of induced pluripotent stem cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. 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 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. These data suggest that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which “captures” their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.

Highlights

► iPSC clones contain hundreds of SNVs that are unique to each clone ► Most iPSC genomes do not contain recurrently mutated genes or pathways ► Reprogramming can select for rare cells with shared genetic variants ► Most SNVs are probably preexisting mutations “captured” by cloning

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