Brief Report: Combined Chemical Treatment Enables Oct4-Induced Reprogramming from Mouse Embryonic Fibroblasts§

Authors

  • Xu Yuan,

    1. Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
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  • Haifeng Wan,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China
    2. Graduate School of Chinese Academy of Sciences, Beijing, People's Republic of China
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  • Xiaoyang Zhao,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China
    2. Graduate School of Chinese Academy of Sciences, Beijing, People's Republic of China
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  • Saiyong Zhu,

    1. Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
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  • Qi Zhou,

    1. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, People's Republic of China
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  • Sheng Ding

    Corresponding author
    1. Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
    • Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA
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    • Telephone: 1-858-784-7376; Fax: 1-858-784-7882


  • Disclosure of potential conflicts of interest is found at the end of this article.

  • Author contributions: X.Y.: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; H.W.: collection and/or assembly of data, data analysis and interpretation; X.Z.: collection and/or assembly of data; S.Z.: collection and/or assembly of data; Q.Z.: conception and design, financial support; S.D.: conception and design, financial support, manuscript writing, final approval of manuscript. X.Y. and H.W. contributed equally to this work.

  • §

    First published online in STEM CELLSEXPRESS January 7, 2011.

Abstract

It has been established that exogenous expression of four transcription factors (Oct4, Klf4, Sox2, and c-Myc) can reprogram mammalian somatic cells to pluripotent states. Further studies demonstrated that such induced pluripotent stem cells (iPSCs) could be generated with fewer exogenous transcription factors, facilitated by endogenous expression of reprogramming factors and/or synthetic small molecules. Here, we reported identification of a new small molecule, a protein arginine methyltransferase inhibitor AMI-5, which enabled Oct4-induced reprogramming of mouse embryonic fibroblasts in combination with transforming growth factor (TGF)-β inhibitor A-83-01. The Oct4-induced iPSCs were shown similar to mouse embryonic stem cells with respect to typical pluripotency criteria. More importantly, they were shown to give rise to liveborn pups through tetraploid complementation assays, demonstrating the high quality of full reprogramming induced by this condition. Furthermore, this study suggests that regulation of protein arginine methylation might be involved in the reprogramming process. STEM CELLS 2011;29:549–553

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