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Induced pluripotent stem (iPS) cells have been generated frommouse and human fibroblasts by the retroviral transduction offour transcription factors. However, the cell origins and molecularmechanisms of iPS cell induction remain elusive. This reportdescribes the generation of iPS cells from adult mouse hepatocytesand gastric epithelial cells. These iPS cell clones appear tobe equivalent to embryonic stem cells in gene expression andare competent to generate germline chimeras. Genetic lineagetracings show that liver-derived iPS cells are derived fromalbumin-expressing cells. No common retroviral integration sitesare found among multiple clones. These data suggest that iPScells are generated by direct reprogramming of lineage-committedsomatic cells and that retroviral integration into specificsites 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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