The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Immortalization eliminates a roadblock during cellular reprogramming into iPS cells
Open accessAbstract
The overexpression of defined transcription factors in somatic cells results in their reprogramming into induced pluripotent stem (iPS) cells. The extremely low efficiency and slow kinetics of in vitro reprogramming suggest that further rare events are required to generate iPS cells. The nature and identity of these events, however, remain elusive. We noticed that the reprogramming potential of primary murine fibroblasts into iPS cells decreases after serial passaging and the concomitant onset of senescence. Consistent with the notion that loss of replicative potential provides a barrier for reprogramming, here we show that cells with low endogenous p19Arf (encoded by the Ink4a/Arf locus, also known as Cdkn2a locus) protein levels and immortal fibroblasts deficient in components of the Arf–Trp53 pathway yield iPS cell colonies with up to threefold faster kinetics and at a significantly higher efficiency than wild-type cells, endowing almost every somatic cell with the potential to form iPS cells. Notably, the acute genetic ablation of Trp53 (also known as p53) in cellular subpopulations that normally fail to reprogram rescues their ability to produce iPS cells. Our results show that the acquisition of immortality is a crucial and rate-limiting step towards the establishment of a pluripotent state in somatic cells and underscore the similarities between induced pluripotency and tumorigenesis.
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Cites
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Self-citationRestoration of p53 function leads to tumour regression in vivo
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Research works printed but not linked: 1
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Cited by
Warren, L., Manos, P. D., Ahfeldt, T., Loh, Y.-H., Li, H., Lau, F., Ebina, W., Mandal, P. K., Smith, Z. D., Meissner, A., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.08.012 · Cited by 2,662
EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
Singh, A., & Settleman, J. (2010) · Oncogene · doi:10.1038/onc.2010.215 · Cited by 2,545
The essence of senescence: Figure 1.
Kuilman, T., Michaloglou, C., Mooi, W. J., & Peeper, D. S. (2010) · Genes & Development · doi:10.1101/gad.1971610 · Cited by 2,038
Cellular Senescence: Aging, Cancer, and Injury
Calcinotto, A., Kohli, J., Zagato, E., Pellegrini, L., Demaria, M., & Alimonti, A. (2019) · Physiological Reviews · doi:10.1152/physrev.00020.2018 · Cited by 1,270
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
Metadata
- Authors
- Utikal, J., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G., & Hochedlinger, K.
- Venue
- Nature
- Published
- 2009-08
- Volume
- 460
- Issue
- 7259
- Pages
- 1145-1148
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2142744987
- Cited by
- 836
- References
- 29
- FWCI
- 43.93
- Type
- journal article
- Language
- en
- Open access
- green
- Licence
- www.springer.com/tdm (tdm)
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- Utikal, J., Polo, J. M., Stadtfeld, M., Maherali, N., Kulalert, W., Walsh, R. M., Khalil, A., Rheinwald, J. G., & Hochedlinger, K. (2009). Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature. https://doi.org/10.1038/nature08285
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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