Research abstract
Letter abstract
Nature Biotechnology 26, 101 - 106 (2008)
Published online: 30 November 2007 | doi:10.1038/nbt1374
Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts
Masato Nakagawa1,5, Michiyo Koyanagi1,5, Koji Tanabe1, Kazutoshi Takahashi1, Tomoko Ichisaka1,2, Takashi Aoi1, Keisuke Okita1, Yuji Mochiduki1, Nanako Takizawa1 & Shinya Yamanaka1,2,3,4
Direct reprogramming of somatic cells provides an opportunity to generate patient- or disease-specific pluripotent stem cells. Such induced pluripotent stem (iPS) cells were generated from mouse fibroblasts by retroviral transduction of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc1. Mouse iPS cells are indistinguishable from embryonic stem (ES) cells in many respects and produce germline-competent chimeras2, 3, 4. Reactivation of the c-Myc retrovirus, however, increases tumorigenicity in the chimeras and progeny mice, hindering clinical applications3. Here we describe a modified protocol for the generation of iPS cells that does not require the Myc retrovirus. With this protocol, we obtained significantly fewer non-iPS background cells, and the iPS cells generated were consistently of high quality. Mice derived from Myc- iPS cells did not develop tumors during the study period. The protocol also enabled efficient isolation of iPS cells without drug selection. Furthermore, we generated human iPS cells from adult dermal fibroblasts without MYC.
- Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
- CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
- Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.
- Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto 606-8507, Japan.
- These authors contributed equally to this work.
Correspondence to: Shinya Yamanaka1,2,3,4 e-mail: yamanaka@frontier.kyoto-u.ac.jp
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