title: Genomic analysis of hESC pedigrees identifies de novo mutations and enables determination of the timing and origin of mutational events.
abstract: Given the association between mutational load and cancer, the observation that genetic aberrations are frequently found in human pluripotent stem cells (hPSCs) is of concern. Prior studies in human induced pluripotent stem cells (hiPSCs) have shown that deletions and regions of loss of heterozygosity (LOH) tend to arise during reprogramming and early culture, whereas duplications more frequently occur during long-term culture. For the corresponding experiments in human embryonic stem cells (hESCs), we studied two sets of hESC lines: one including the corresponding parental DNA and the other generated from single blastomeres from four sibling embryos. Here, we show that genetic aberrations observed in hESCs can originate during preimplantation embryo development and/or early derivation. These early aberrations are mainly deletions and LOH, whereas aberrations arising during long-term culture of hESCs are more frequently duplications. Our results highlight the importance of close monitoring of genomic integrity and the development of improved methods for derivation and culture of hPSCs.
authors.affiliation: Wolfe PGD Stem Cell Lab, Racine IVF Unit, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv 64239, Israel; Department of Cell and Developmental Biology, Sackler Medical School, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Dalit
authors.initials: D
authors.lastname: Ben-Yosef
authors.forename: Francesca S
authors.initials: FS
authors.lastname: Boscolo
authors.forename: Hadar
authors.initials: H
authors.lastname: Amir
authors.forename: Mira
authors.initials: M
authors.lastname: Malcov
authors.forename: Ami
authors.initials: A
authors.lastname: Amit
authors.forename: Louise C
authors.initials: LC
authors.lastname: Laurent
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D023281:Genomics / Q000379:methods*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D009154:Mutation; D010375:Pedigree; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000473:pathology / Q000502:physiology*
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