@article{4ad155bfc8ec4325ba628f38a0c815ac,
title = "Background mutations in parental cells account for most of the genetic heterogeneity of induced pluripotent stem cells",
abstract = "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.",
author = "Young, {Margaret A.} and Larson, {David E.} and Sun, {Chiao Wang} and George, {Daniel R.} and Li Ding and Miller, {Christopher A.} and Ling Lin and Pawlik, {Kevin M.} and Ken Chen and Xian Fan and Heather Schmidt and Joelle Kalicki-Veizer and Cook, {Lisa L.} and Swift, {Gary W.} and Demeter, {Ryan T.} and Wendl, {Michael C.} and Sands, {Mark S.} and Mardis, {Elaine R.} and Wilson, {Richard K.} and Townes, {Tim M.} and Ley, {Timothy J.}",
note = "Funding Information: The authors thank the Siteman Cancer Center Embryonic Stem Cell Core, the Molecular and Genomic Analysis Core, and the Flow Cytometry Core for their expert contributions to this work. We would like to acknowledge the Analysis Pipeline group at the Genome Institute for developing the automated sequence analysis pipelines and Joshua McMichael for his assistance in figure design. We thank Drs. Suellen Greco, Jeffery Klco, and Trenton Shoeb for carefully reviewing the teratoma pathology. This work was funded by grants to R.K.W. from the National Human Genome Research Institute (NHGRI U54 HG003079), T.M.T. from the National Heart Lung and Blood Institute (HL057619), and T.J.L. from the National Institutes of Health (CA0101937 and DK38682) and the Barnes-Jewish Hospital Foundation. ",
year = "2012",
month = may,
day = "4",
doi = "10.1016/j.stem.2012.03.002",
language = "English (US)",
volume = "10",
pages = "570--582",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "5",
}