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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}

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