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Cited by 129Pluripotent Stem Cells ResearchCRISPR and Genetic EngineeringEpigenetics and DNA Methylation

Whole-genome mutational burden analysis of three pluripotency induction methods

Open access
Bhutani, Kunal, Nazor, Kristopher L., Williams, Roy, Tran, Ha, Dai, Heng, Džakula, Željko, Cho, Edward H., Pang, Andy W. C. +4 more·2016·Nature Communications
DOI 10.1038/ncomms10536PMC PMC4762882
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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.

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  • High reprogramming efficiency without genomic integration of the SeV vector was demonstrated commercially.

    “The high reprogramming efficiency without genomic integration of the SeV vector was also demonstrated commercially [140].”

    From Non-Integrating Lentiviral Vectors in Clinical Applications: A Glance Through (2022) · cites this paper as [140]

    The Discussion (page not provided) describes Sendai viral vectors as non-integrating delivery methods that have become more efficient. The Methods, under “Sendai virus reprogramming” (page not provided), report using a commercial Sendai kit to generate iPSC colonies. The paper does not establish that this commercial kit had high reprogramming efficiency. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cites

Flagged first, then by citations

Research works printed but not linked: 24

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Authors
Bhutani, K., Nazor, K. L., Williams, R., Tran, H., Dai, H., Džakula, Ž., Cho, E. H., Pang, A. W. C., Rao, M., Cao, H., Schork, N. J., & Loring, J. F.
Affiliations
  • Scripps Research Institute (US)
  • BioNano Genomics (United States) (US)
  • National Institutes of Health (US)
Corresponding author
  • Schork, Nicholas J.
  • Loring, Jeanne F.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2016-02-19
Volume
7
Issue
1
Pages
10536-10536
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/ncomms10536
PMC
PMC4762882
OpenAlex
W2278911990
Cited by
129
References
2
Citations by year
2026: 5 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 11 · 2021: 13 · 2020: 13 · 2019: 17 · 2018: 11 · 2017: 20 · 2016: 20
FWCI
11.78
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (1144086)
  • Autism Speaks
  • California Institute for Regenerative Medicine (RT1-01108, CL1‐00502, TR3-05603, TR1-01250, RT3-07655)
  • National Institutes of Health (DGE1144086, AG023122)
  • National Institute on Aging (R21AG045789, U19AG023122)
  • National Institute of Mental Health (R33MH087925)
  • Common Fund
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
induced pluripotent stem cells, mutational burden, retroviral vectors, Sendai virus, synthetic mRNA, single nucleotide variants, indels, structural variants, isogenic iPSC lines, fibroblast reprogramming, cell therapy safety
MeSH terms
Cell Differentiation, DNA Mutational Analysis, Fibroblasts, Humans, Mutation, Genome, Genomics, Induced Pluripotent Stem Cells

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