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.

journal_name

Cell Stem Cell

journal_title

Cell stem cell

authors

Young MA,Larson DE,Sun CW,George DR,Ding L,Miller CA,Lin L,Pawlik KM,Chen K,Fan X,Schmidt H,Kalicki-Veizer J,Cook LL,Swift GW,Demeter RT,Wendl MC,Sands MS,Mardis ER,Wilson RK,Townes TM,Ley TJ

doi

10.1016/j.stem.2012.03.002

subject

Has Abstract

pub_date

2012-05-04 00:00:00

pages

570-82

issue

5

eissn

1934-5909

issn

1875-9777

pii

S1934-5909(12)00119-1

journal_volume

10

pub_type

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