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Genome Sequences Reveal Range Mutations in Induced Pluripotent Stem Cells

In Nature Genetics, investigators at the Wellcome Sanger Institute, the University of Cambridge, and elsewhere share findings from a whole-genome sequencing- or exome sequencing-based analysis of almost 700 human induced pluripotent stem cells (iPSCs) or subclones derived from distinct tissue types. After identifying distinct mutation loads and mutational signatures in fibroblast- or blood-derived iPSCs from one individual, the team went on to analyze genome sequences for 696 human iPSCs or daughter subclones, confirming that iPSCs produced from skin fibroblasts had higher mutation rates than those derived from blood samples. Although more than 70 percent of the fibroblast-derived iPSCs had mutations related to ultraviolet light damage, for example, the researchers also saw significant differences between different fibroblast-derived iPSC clones. Even so, they note, both fibroblast- and blood-derived iPSCs appeared prone to culture-related oxidative DNA damage, along with BCOR mutations that influenced gene expression and differentiation in the cells and appeared to be subject to selection pressure. "Our work highlights best practice points to consider when establishing [human iPSC] cellular models: an originating somatic cell type with low levels of preexisting genomic damage and minimizing duration of cell culture," the authors report.