| Literature DB >> 27151456 |
Eunju Kang1, Xinjian Wang2, Rebecca Tippner-Hedges1, Hong Ma1, Clifford D L Folmes3, Nuria Marti Gutierrez1, Yeonmi Lee1, Crystal Van Dyken1, Riffat Ahmed1, Ying Li1, Amy Koski1, Tomonari Hayama1, Shiyu Luo2, Cary O Harding4, Paula Amato5, Jeffrey Jensen5, David Battaglia5, David Lee5, Diana Wu5, Andre Terzic3, Don P Wolf1, Taosheng Huang6, Shoukhrat Mitalipov7.
Abstract
The genetic integrity of iPSCs is an important consideration for therapeutic application. In this study, we examine the accumulation of somatic mitochondrial genome (mtDNA) mutations in skin fibroblasts, blood, and iPSCs derived from young and elderly subjects (24-72 years). We found that pooled skin and blood mtDNA contained low heteroplasmic point mutations, but a panel of ten individual iPSC lines from each tissue or clonally expanded fibroblasts carried an elevated load of heteroplasmic or homoplasmic mutations, suggesting that somatic mutations randomly arise within individual cells but are not detectable in whole tissues. The frequency of mtDNA defects in iPSCs increased with age, and many mutations were non-synonymous or resided in RNA coding genes and thus can lead to respiratory defects. Our results highlight a need to monitor mtDNA mutations in iPSCs, especially those generated from older patients, and to examine the metabolic status of iPSCs destined for clinical applications.Entities:
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Year: 2016 PMID： 27151456 DOI： 10.1016/j.stem.2016.02.005
Source DB: PubMed Journal: Cell Stem Cell ISSN： 1875-9777 Impact factor: 24.633