Whole-genome mutational burden analysis of three pluripotency induction methods

Kunal Bhutani, Kristopher L. Nazor, Roy Williams, Ha Tran, Heng Dai, Željko Džakula, Edward H. Cho, Andy W. C. Pang, Mahendra Rao, Han Cao, Nicholas J. Schork () and Jeanne F. Loring ()
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Kunal Bhutani: Scripps Translational Science Institute and The Scripps Research Institute
Kristopher L. Nazor: The Scripps Research Institute, Center for Regenerative Medicine
Roy Williams: The Scripps Research Institute, Center for Regenerative Medicine
Ha Tran: The Scripps Research Institute, Center for Regenerative Medicine
Heng Dai: BioNano Genomics
Željko Džakula: BioNano Genomics
Edward H. Cho: BioNano Genomics
Andy W. C. Pang: BioNano Genomics
Mahendra Rao: The National Institutes of Health
Han Cao: BioNano Genomics
Nicholas J. Schork: Scripps Translational Science Institute and The Scripps Research Institute
Jeanne F. Loring: The Scripps Research Institute, Center for Regenerative Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: Abstract There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming methods: integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs. We used whole-genome sequencing and de novo genome mapping to identify single-nucleotide variants, insertions and deletions, and structural variants. Our results show a moderate number of variants in the iPSCs that were not evident in the parental fibroblasts, which may result from reprogramming. There were only small differences in the total numbers and types of variants among different reprogramming methods. Most importantly, a thorough genomic analysis showed that the variants were generally benign. We conclude that the process of reprogramming is unlikely to introduce variants that would make the cells inappropriate for therapy.

Date: 2016
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DOI: 10.1038/ncomms10536

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