The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Virus-free induction of pluripotency and subsequent excision of reprogramming factors
Open accessAbstract
Reprogramming of somatic cells to pluripotency, thereby creating induced pluripotent stem (iPS) cells, promises to transform regenerative medicine. Most instances of direct reprogramming have been achieved by forced expression of defined factors using multiple viral vectors. However, such iPS cells contain a large number of viral vector integrations, any one of which could cause unpredictable genetic dysfunction. Whereas c-Myc is dispensable for reprogramming, complete elimination of the other exogenous factors is also desired because ectopic expression of either Oct4 (also known as Pou5f1) or Klf4 can induce dysplasia. Two transient transfection-reprogramming methods have been published to address this issue. However, the efficiency of both approaches is extremely low, and neither has been applied successfully to human cells so far. Here we show that non-viral transfection of a single multiprotein expression vector, which comprises the coding sequences of c-Myc, Klf4, Oct4 and Sox2 linked with 2A peptides, can reprogram both mouse and human fibroblasts. Moreover, the transgene can be removed once reprogramming has been achieved. iPS cells produced with this non-viral vector show robust expression of pluripotency markers, indicating a reprogrammed state confirmed functionally by in vitro differentiation assays and formation of adult chimaeric mice. When the single-vector reprogramming system was combined with a piggyBac transposon, we succeeded in establishing reprogrammed human cell lines from embryonic fibroblasts with robust expression of pluripotency markers. This system minimizes genome modification in iPS cells and enables complete elimination of exogenous reprogramming factors, efficiently providing iPS cells that are applicable to regenerative medicine, drug screening and the establishment of disease models.
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Cites
Takahashi, K., & Yamanaka, S. (2006) · Cell · doi:10.1016/j.cell.2006.07.024 · Cited by 26,673
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221
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
Efficient selection for high-expression transfectants with a novel eukaryotic vector
Hitoshi, N., Ken-ichi, Y., & Jun-ichi, M. (1991) · Gene · doi:10.1016/0378-1119(91)90434-d · Cited by 5,134
Generation of germline-competent induced pluripotent stem cells
Okita, K., Ichisaka, T., & Yamanaka, S. (2007) · Nature · doi:10.1038/nature05934 · Cited by 4,299
In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state
Wernig, M., Meissner, A., Foreman, R., Brambrink, T., Ku, M., Hochedlinger, K., Bernstein, B. E., & Jaenisch, R. (2007) · Nature · doi:10.1038/nature05944 · Cited by 2,676
Reprogramming of human somatic cells to pluripotency with defined factors
Park, I.-H., Zhao, R., West, J. A., Yabuuchi, A., Huo, H., Ince, T. A., Lerou, P. H., Lensch, M. W., & Daley, G. Q. (2008) · Nature · doi:10.1038/nature06534 · Cited by 2,436
Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts
Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., Okita, K., Mochiduki, Y., Takizawa, N., & Yamanaka, S. (2008) · Nature Biotechnology · doi:10.1038/nbt1374 · Cited by 2,380
Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors
Okita, K., Nakagawa, M., Hyenjong, H., Ichisaka, T., & Yamanaka, S. (2008) · Science · doi:10.1126/science.1164270 · Cited by 2,009
piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells
Woltjen, K., Michael, I. P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., Cowling, R., Wang, W., Liu, P., Gertsenstein, M., et al. (2009) · Nature · doi:10.1038/nature07863 · Cited by 1,814
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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
Human induced pluripotent stem cells free of vector and transgene sequences
Yu, J., Hu, K., Smuga-Otto, K., Tian, S., Stewart, R., Slukvin, I. I., & Thomson, J. A. (2009) · Science · doi:10.1126/science.1172482 · Cited by 2,386
Generation of Human Induced Pluripotent Stem Cells by Direct Delivery of Reprogramming Proteins
Kim, D., Kim, C.-H., Moon, J.-I., Chung, Y.-G., Chang, M.-Y., Han, B.-S., Ko, S., Yang, E., Cha, K. Y., Lanza, R., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.05.005 · Cited by 1,814
Generation of Induced Pluripotent Stem Cells Using Recombinant Proteins
Zhou, H., Wu, S., Joo, J. Y., Zhu, S., Han, D. W., Lin, T., Trauger, S., Bien, G., Yao, S., Zhu, Y., et al. (2009) · Cell stem cell · doi:10.1016/j.stem.2009.04.005 · Cited by 1,788
FUSAKI, N., BAN, H., NISHIYAMA, A., SAEKI, K., & HASEGAWA, M. (2009) · Proceedings of the Japan Academy Series B · doi:10.2183/pjab.85.348 · Cited by 1,411
Metadata
- Authors
- Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., & Woltjen, K.
- Venue
- Nature
- Published
- 2009-03-01
- Volume
- 458
- Issue
- 7239
- Pages
- 771-775
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2106485710
- Cited by
- 1,251
- References
- 28
- FWCI
- 78.50
- Type
- journal article
- Language
- en
- Open access
- green
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