Whole-genome mutational burden analysis of three pluripotency induction methods

• Published in: Nature communications Vol. 7; no. 1; p. 10536
• Main Authors: Bhutani, Kunal, Nazor, Kristopher L., Williams, Roy, Tran, Ha, Dai, Heng, Džakula, Željko, Cho, Edward H., Pang, Andy W. C., Rao, Mahendra, Cao, Han, Schork, Nicholas J., Loring, Jeanne F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.02.2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/106; 631/136/532/2064/2158; 631/136/532/2435; 631/61/212; 631/61/51/1844/2319; Cell Differentiation; DNA Mutational Analysis - methods; Fibroblasts - chemistry; Fibroblasts - cytology; Gene mapping; Genome; Genomes; Genomics; Genomics - methods; Humanities and Social Sciences; Humans; Induced Pluripotent Stem Cells - chemistry; Induced Pluripotent Stem Cells - cytology; multidisciplinary; Mutation; Science; Science (multidisciplinary); Stem cells; New York; La Jolla California; California; United States > US
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10536

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. It is feared that reprogramming may introduce DNA mutations. Here Bhutani et al . take three different reprogramming methods and using comparative whole genome analyses do identify nucleotide variations that are different in reprogrammed cells from the original fibroblasts, but none convey oncogenic potential.