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Nuclear reprogramming to a pluripotent state by three approaches

Abstract

The stable states of differentiated cells are now known to be controlled by dynamic mechanisms that can easily be perturbed. An adult cell can therefore be reprogrammed, altering its pattern of gene expression, and hence its fate, to that typical of another cell type. This has been shown by three distinct experimental approaches to nuclear reprogramming: nuclear transfer, cell fusion and transcription-factor transduction. Using these approaches, nuclei from 'terminally differentiated' somatic cells can be induced to express genes that are typical of embryonic stem cells, which can differentiate to form all of the cell types in the body. This remarkable discovery of cellular plasticity has important medical applications.

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Figure 1: Three approaches to nuclear reprogramming to pluripotency.
Figure 2: Timeline of discoveries in nuclear reprogramming.
Figure 3: Investigating the genes involved in nuclear reprogramming by using mixed-species heterokaryons.
Figure 4: Applications of iPS cells.
Figure 5: Comparison of the advantages of the three approaches to nuclear reprogramming.

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Acknowledgements

We apologize to those whose work is not cited because of space constraints. We are grateful to our colleagues J. Gurdon, T. Graf, J. Pomerantz and T. Tada, as well as to members of our laboratories for their insightful comments on the manuscript and especially to N. Bhutani and S. Corbel for figure design. We also thank our funding sources: S.Y. acknowledges support from the Japanese Ministry of Education, Culture, Sports, Science & Technology, the Japan Science and Technology Agency and the National Institute of Biomedical Innovation (Japan); and H.M.B. acknowledges support from the National Institutes of Health (grants AG009521, AG020961 and HL096113), MDA (4320), the Juvenile Diabetes Research Foundation (34-2008-623), LLS (6025-09), the California Institute for Regenerative Medicine (RT1-01001 and RB1-02192) and the Baxter International Foundation.

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Yamanaka, S., Blau, H. Nuclear reprogramming to a pluripotent state by three approaches. Nature 465, 704–712 (2010). https://doi.org/10.1038/nature09229

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