Abstract
Reprogramming of mouse and human somatic cells can be achieved by ectopic expression of transcription factors, but with low efficiencies. We report that DNA methyltransferase and histone deacetylase (HDAC) inhibitors improve reprogramming efficiency. In particular, valproic acid (VPA), an HDAC inhibitor, improves reprogramming efficiency by more than 100-fold, using Oct4-GFP as a reporter. VPA also enables efficient induction of pluripotent stem cells without introduction of the oncogene c-Myc.
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Acknowledgements
D.A.M. is a Howard Hughes Medical Institute Investigator. D.H. is funded by the Helen Hay Whitney Foundation and Novartis Institutes for BioMedical Research. W.G. is funded by the Susan G. Komen Breast Cancer Foundation. A.E.C. is supported by the Jane Coffin Childs Memorial Fund for Medical Research and Merck Research Laboratories. The authors would like to thank J. Lamenzo and A. Kweudjeu for assistance with micoarray analysis, S. Chen for insightful discussions and critical review of the manuscript. We would also like to thank R. Weinberg for support of this study. Some monoclonal antibodies were obtained from the Developmental Studies Hybridoma Bank, which was developed under the auspices of the National Institute of Child Health and Human Development and is maintained by The University of Iowa, Department of Biological Sciences.
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D.H. and D.A.M. conceived the experiments and wrote the manuscript. D.H., R.M., W.G., A.E., M.S. and A.E.C. performed experiments.
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Huangfu, D., Maehr, R., Guo, W. et al. Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds. Nat Biotechnol 26, 795–797 (2008). https://doi.org/10.1038/nbt1418
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DOI: https://doi.org/10.1038/nbt1418
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