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.
authors.affiliation: Department of Internal Medicine, Division of Oncology, Section of Stem Cell Biology, Washington University, St Louis, MO 63110, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Young
authors.forename: David E
authors.initials: DE
authors.lastname: Larson
authors.forename: Chiao-Wang
authors.initials: CW
authors.lastname: Sun
authors.forename: Daniel R
authors.initials: DR
authors.lastname: George
authors.forename: Li
authors.initials: L
authors.lastname: Ding
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Miller
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Pawlik
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.forename: Xian
authors.initials: X
authors.lastname: Fan
authors.forename: Heather
authors.initials: H
authors.lastname: Schmidt
authors.forename: Joelle
authors.initials: J
authors.lastname: Kalicki-Veizer
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Cook
authors.forename: Gary W
authors.initials: GW
authors.lastname: Swift
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Demeter
authors.forename: Michael C
authors.initials: MC
authors.lastname: Wendl
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sands
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Mardis
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Ley
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002999:Clone Cells; D004247:DNA / Q000032:analysis / Q000235:genetics; D042822:Genomic Instability; D048091:Guided Tissue Regeneration / Q000379:methods / Q000592:standards; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D044968:Regenerative Medicine
chemical_list: D004247:DNA