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Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells
Open accessAbstract
Summary To assess the genetic consequences of induced Pluripotent Stem Cell (iPSC) reprogramming, we sequenced the genomes of ten murine iPSC clones derived from three independent reprogramming experiments, and compared them to their parental cell genomes. We detected hundreds of single nucleotide variants (SNVs) in every clone, with an average of 11 in coding regions. In two experiments, all SNVs were unique for each clone and did not cluster in pathways, but in the third, all four iPSC clones contained 157 shared genetic variants, which could also be detected in rare cells (<1 in 500) within the parental MEF pool. This data suggests that most of the genetic variation in iPSC clones is not caused by reprogramming per se, but is rather a consequence of cloning individual cells, which “captures” their mutational history. These findings have implications for the development and therapeutic use of cells that are reprogrammed by any method.
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Cites
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Yu, J., Vodyanik, M. A., Smuga-Otto, K., Antosiewicz-Bourget, J., Frane, J. L., Tian, S., Nie, J., Jonsdottir, G. A., Ruotti, V., Stewart, R., et al. (2007) · Science · doi:10.1126/science.1151526 · Cited by 10,310
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Somatic coding mutations in human induced pluripotent stem cells
Gore, A., Li, Z., Fung, H.-L., Young, J. E., Agarwal, S., Antosiewicz-Bourget, J., Canto, I., Giorgetti, A., Israel, M. A., Kiskinis, E., et al. (2011) · Nature · doi:10.1038/nature09805 · Cited by 1,273
Laurent, L. C., Ulitsky, I., Slavin, I., Tran, H., Schork, A., Morey, R., Lynch, C., Harness, J. V., Lee, S., Barrero, M. J., et al. (2011) · Cell stem cell · doi:10.1016/j.stem.2010.12.003 · Cited by 890
Cited by
The origin and evolution of mutations in acute myeloid leukemia
Welch, J. S., Ley, T. J., Link, D. C., Miller, C. A., Larson, D. E., Koboldt, D. C., Wartman, L. D., Lamprecht, T. L., Liu, F., Xia, J., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.023 · Cited by 1,575
Self-citationInduced Pluripotent Stem Cells: Past, Present, and Future
Yamanaka, S. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.05.005 · Cited by 843
Induced pluripotent stem cells: the new patient?
Bellin, M., Marchetto, M. C., Gage, F. H., & Mummery, C. L. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3448 · Cited by 431
Differences between germline and somatic mutation rates in humans and mice
Milholland, B., Dong, X., Zhang, L., Hao, X., Suh, Y., & Vijg, J. (2017) · Nature Communications · doi:10.1038/ncomms15183 · Cited by 429
Genetic and Epigenetic Variations in iPSCs: Potential Causes and Implications for Application
Liang, G., & Zhang, Y. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.07.001 · Cited by 369
Metadata
- Authors
- Young, M. A., Larson, D. E., Sun, C.-W., George, D. R., Ding, L., Miller, C. A., Lin, L., Pawlik, K. M., Chen, K., Fan, X., Schmidt, H., Kalicki-Veizer, J., Cook, L. L., Swift, G. W., Demeter, R. T., Wendl, M. C., Sands, M. S., Mardis, E. R., Wilson, R. K., Townes, T. M., & Ley, T. J.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 10
- Issue
- 5
- Pages
- 570-582
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2052159842
- Cited by
- 197
- References
- 4
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Young, M. A., Larson, D. E., Sun, C.-W., George, D. R., Ding, L., Miller, C. A., Lin, L., Pawlik, K. M., Chen, K., Fan, X., Schmidt, H., Kalicki-Veizer, J., Cook, L. L., Swift, G. W., Demeter, R. T., Wendl, M. C., Sands, M. S., Mardis, E. R., Wilson, R. K., . . . Ley, T. J. (2012). Background Mutations in Parental Cells Account for Most of the Genetic Heterogeneity of Induced Pluripotent Stem Cells. Cell Stem Cell. https://doi.org/10.1016/j.stem.2012.03.002
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
