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      Induction of pluripotent stem cells by defined factors is greatly improved by small molecule compounds

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          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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          Author and article information

          Journal
          9604648
          20305
          Nat Biotechnol
          Nat. Biotechnol.
          Nature biotechnology
          1087-0156
          1546-1696
          9 January 2019
          22 June 2008
          July 2008
          16 January 2019
          : 26
          : 7
          : 795-797
          Affiliations
          [1 ]Department of Stem Cell and Regenerative Biology, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA
          [2 ]Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.
          [3 ]Biomedical Sciences, Utrecht University, The Netherlands
          Author notes

          Author Contributions

          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.

          Correspondence should be addressed to D.A.M. ( dmelton@ 123456harvard.edu ).
          Article
          PMC6334647 PMC6334647 6334647 hhmipa1002247
          10.1038/nbt1418
          6334647
          18568017
          4480ce04-47fa-41ca-a9e6-c7de33825a99
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