Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf41. However, the conversion to iPSCs is inefficient. The proto-oncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs2. Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal–epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.
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We thank T. Yamamoto, Y. Yamada and the members of our laboratory for valuable scientific discussions and administrative support. We thank M. Nakagawa, H. Seki, M. Murakami, A. Okada, M. Narita, M. Inoue, H. Shiga and T. Matsumoto for technical assistance and H. Suemori (Kyoto University) for human ES cells. This work was supported in part by grants from the New Energy and Industrial Technology Development Organization (NEDO), the Leading Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), the Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) of the Japanese Society for the Promotion of Science (JSPS), Grants-in-Aid for Scientific Research from JSPS and MEXT, and the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO). S.Y. is a member of scientific advisory boards of iPearian Inc. and iPS Academia Japan.
The authors declare no competing financial interests.
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Maekawa, M., Yamaguchi, K., Nakamura, T. et al. Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1. Nature 474, 225–229 (2011). https://doi.org/10.1038/nature10106
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