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Science 321 (5889): 699-702

Copyright © 2008 by the American Association for the Advancement of Science

Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells

Takashi Aoi,1,2 Kojiro Yae,1 Masato Nakagawa,1 Tomoko Ichisaka,1,3 Keisuke Okita,1 Kazutoshi Takahashi,1 Tsutomu Chiba,2 Shinya Yamanaka1,3,4,5*

Abstract: Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.

1 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
2 Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
3 Core Research in Embryonic Science and Technology (CREST), Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
4 Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
5 Center for Induced Pluripotent Stem (iPS) Cell Research and Application, Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.

* To whom correspondence should be addressed. E-mail: yamanaka{at}frontier.kyoto-u.ac.jp

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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T. Ezashi, B. P. V. L. Telugu, A. P. Alexenko, S. Sachdev, S. Sinha, and R. M. Roberts (2009)
PNAS 106, 10993-10998
   Abstract »    Full Text »    PDF »
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M. A. Esteban, J. Xu, J. Yang, M. Peng, D. Qin, W. Li, Z. Jiang, J. Chen, K. Deng, M. Zhong, et al. (2009)
J. Biol. Chem. 284, 17634-17640
   Abstract »    Full Text »    PDF »
Induced pluripotent stem cells offer new approach to therapy in thalassemia and sickle cell anemia and option in prenatal diagnosis in genetic diseases.
L. Ye, J. C. Chang, C. Lin, X. Sun, J. Yu, and Y. W. Kan (2009)
PNAS 106, 9826-9830
   Abstract »    Full Text »    PDF »
Generation of mouse-induced pluripotent stem cells by transient expression of a single nonviral polycistronic vector.
F. Gonzalez, M. Barragan Monasterio, G. Tiscornia, N. Montserrat Pulido, R. Vassena, L. Batlle Morera, I. Rodriguez Piza, and J. C. I. Belmonte (2009)
PNAS 106, 8918-8922
   Abstract »    Full Text »    PDF »
Phenobarbital Elicits Unique, Early Changes in the Expression of Hepatic Genes that Affect Critical Pathways in Tumor-Prone B6C3F1 Mice.
J. M. Phillips, L. D. Burgoon, and J. I. Goodman (2009)
Toxicol. Sci. 109, 193-205
   Abstract »    Full Text »    PDF »
Reprogramming to a muscle fate by fusion recapitulates differentiation.
J. H. Pomerantz, S. Mukherjee, A. T. Palermo, and H. M. Blau (2009)
J. Cell Sci. 122, 1045-1053
   Abstract »    Full Text »    PDF »
Multiple Genes Exhibit Phenobarbital-Induced Constitutive Active/Androstane Receptor-Mediated DNA Methylation Changes during Liver Tumorigenesis and in Liver Tumors.
J. M. Phillips and J. I. Goodman (2009)
Toxicol. Sci. 108, 273-289
   Abstract »    Full Text »    PDF »
Klf4 reverts developmentally programmed restriction of ground state pluripotency.
G. Guo, J. Yang, J. Nichols, J. S. Hall, I. Eyres, W. Mansfield, and A. Smith (2009)
Development 136, 1063-1069
   Abstract »    Full Text »    PDF »
Functional Cardiomyocytes Derived From Human Induced Pluripotent Stem Cells.
J. Zhang, G. F. Wilson, A. G. Soerens, C. H. Koonce, J. Yu, S. P. Palecek, J. A. Thomson, and T. J. Kamp (2009)
Circ. Res. 104, e30-e41
   Abstract »    Full Text »    PDF »
Epigenetic reprogramming and induced pluripotency.
K. Hochedlinger and K. Plath (2009)
Development 136, 509-523
   Abstract »    Full Text »    PDF »
Cellular Cardiomyoplasty: What Have We Learned?.
R. L. Kao, W. Browder, and C. Li (2009)
Asian Cardiovascular and Thoracic Annals 17, 89-101
   Abstract »    Full Text »    PDF »
Common Themes of Dedifferentiation in Somatic Cell Reprogramming and Cancer.
G.Q. Daley (2009)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Nuclear Reprogramming in Cells.
J. B. Gurdon and D. A. Melton (2008)
Science 322, 1811-1815
   Abstract »    Full Text »    PDF »
Of Germ Cells, Trophoblasts, and Cancer Stem Cells.
A. R. Burleigh (2008)
Integr Cancer Ther 7, 276-281
   Abstract »    PDF »
The significance of induced pluripotent stem cells for basic research and clinical therapy.
J R Meyer (2008)
J. Med. Ethics 34, 849-851
   Abstract »    Full Text »    PDF »
Mouse Meningiocytes Express Sox2 and Yield High Efficiency of Chimeras after Nuclear Reprogramming with Exogenous Factors.
D. Qin, Y. Gan, K. Shao, H. Wang, W. Li, T. Wang, W. He, J. Xu, Y. Zhang, Z. Kou, et al. (2008)
J. Biol. Chem. 283, 33730-33735
   Abstract »    Full Text »    PDF »
Induced Pluripotent Stem Cells Generated Without Viral Integration.
M. Stadtfeld, M. Nagaya, J. Utikal, G. Weir, and K. Hochedlinger (2008)
Science 322, 945-949
   Abstract »    Full Text »    PDF »
Generation of Mouse Induced Pluripotent Stem Cells Without Viral Vectors.
K. Okita, M. Nakagawa, H. Hyenjong, T. Ichisaka, and S. Yamanaka (2008)
Science 322, 949-953
   Abstract »    Full Text »    PDF »
Induced Pluripotency of Mouse and Human Somatic Cells.
N. Maherali and K. Hochedlinger (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Reprogramming of Somatic Cell Identity.
J. Hanna, B.W. Carey, and R. Jaenisch (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Mapping Key Features of Transcriptional Regulatory Circuitry in Embryonic Stem Cells.
M.F. Cole and R.A. Young (2008)
Cold Spring Harb Symp Quant Biol
   Abstract »    PDF »
Pluripotent stem cell lines.
J. Yu and J. A. Thomson (2008)
Genes & Dev. 22, 1987-1997
   Abstract »    Full Text »    PDF »

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