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A decade of transcription factor-mediated reprogramming to pluripotency

Nature Reviews Molecular Cell Biology volume 17, pages 183–193 (2016)Cite this article

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Abstract

The past 10 years have seen great advances in our ability to manipulate cell fate, including the induction of pluripotency in vitro to generate induced pluripotent stem cells (iPSCs). This process proved to be remarkably simple from a technical perspective, only needing the host cell and a defined cocktail of transcription factors, with four factors — octamer-binding protein 3/4 (OCT3/4), SOX2, Krüppel-like factor 4 (KLF4) and MYC (collectively referred to as OSKM) — initially used. The mechanisms underlying transcription factor-mediated reprogramming are still poorly understood; however, several mechanistic insights have recently been obtained. Recent years have also brought significant progress in increasing the efficiency of this technique, making it more amenable to applications in the fields of regenerative medicine, disease modelling and drug discovery.

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Figure 1: Early studies of cell fate plasticity.
Figure 2: The timeline of reprogramming and induced pluripotency research.
Figure 3: Mechanistic insights into transcription factor-mediated reprogramming towards pluripotency.

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Acknowledgements

The authors would like to thank all Yamanaka laboratory members, past and present, and are also grateful to Y. Miyake, R. Kato, E. Minamitani, S. Takeshima, R. Fujiwara, H. Imagawa and Y. Uematsu for their administrative support, and P. Karagiannis for crucial reading of the manuscript. This work was supported by Grants-in-Aid for Scientific Research from the Japanese Society for the Promotion of Science (JSPS) and the Ministry of Education, Culture, Sports, Science and Technology (MEXT); a grant from the Leading Project of the MEXT; a grant from the Funding Program for World-Leading Innovative Research and Development in Science and Technology (First Program) of the JSPS; a grant from the Core Center for iPS Cell Research, Research Center Network for Realization of Regenerative Medicine; a grant from the World Premier International Research Center Initiative (WPI), MEXT; a grant from the Japan Foundation for Applied Enzymology; and the iPS Cell Research Fund.

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  1. Kazutoshi Takahashi and Shinya Yamanaka are at the Center for iPS Cell Research and Application, Kyoto University, Kyoto, 606–8507, Japan, and the Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, California 94158, USA.,

    Kazutoshi Takahashi & Shinya Yamanaka

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Correspondence to Kazutoshi Takahashi or Shinya Yamanaka.

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Shinya Yamanaka is a scientific advisor of iPS Academia Japan without salary.

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Takahashi, K., Yamanaka, S. A decade of transcription factor-mediated reprogramming to pluripotency. Nat Rev Mol Cell Biol 17, 183–193 (2016). https://doi.org/10.1038/nrm.2016.8

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