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IPSCs and fibroblast subclones from the same fibroblast population contain comparable levels of sequence variations.


ABSTRACT: Genome integrity of induced pluripotent stem cells (iPSCs) has been extensively studied in recent years, but it is still unclear whether iPSCs contain more genomic variations than cultured somatic cells. One important question is the origin of genomic variations detected in iPSCs-whether iPSC reprogramming induces such variations. Here, we undertook a unique approach by deriving fibroblast subclones and clonal iPSC lines from the same fibroblast population and applied next-generation sequencing to compare genomic variations in these lines. Targeted deep sequencing of parental fibroblasts revealed that most variants detected in clonal iPSCs and fibroblast subclones were rare variants inherited from the parental fibroblasts. Only a small number of variants remained undetectable in the parental fibroblasts, which were thus likely to be de novo. Importantly, the clonal iPSCs and fibroblast subclones contained comparable numbers of de novo variants. Collectively, our data suggest that iPSC reprogramming is not mutagenic.

SUBMITTER: Kwon EM 

PROVIDER: S-EPMC5338363 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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iPSCs and fibroblast subclones from the same fibroblast population contain comparable levels of sequence variations.

Kwon Erika M EM   Connelly John P JP   Hansen Nancy F NF   Donovan Frank X FX   Winkler Thomas T   Davis Brian W BW   Alkadi Halah H   Chandrasekharappa Settara C SC   Dunbar Cynthia E CE   Mullikin James C JC   Liu Paul P  

Proceedings of the National Academy of Sciences of the United States of America 20170206 8


Genome integrity of induced pluripotent stem cells (iPSCs) has been extensively studied in recent years, but it is still unclear whether iPSCs contain more genomic variations than cultured somatic cells. One important question is the origin of genomic variations detected in iPSCs-whether iPSC reprogramming induces such variations. Here, we undertook a unique approach by deriving fibroblast subclones and clonal iPSC lines from the same fibroblast population and applied next-generation sequencing  ...[more]

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