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Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells

Nature Biotechnology volume 25, pages 1177–1181 (2007)Cite this article

Abstract

In vitro reprogramming of somatic cells into a pluripotent embryonic stem cell–like state has been achieved through retroviral transduction of murine fibroblasts with Oct4, Sox2, c-myc and Klf4 (refs. 1,2,3,4). In these experiments, the rare 'induced pluripotent stem' (iPS) cells were isolated by stringent selection for activation of a neomycin-resistance gene inserted into the endogenous Oct4 (also known as Pou5f1) or Nanog loci2,3,4. Direct isolation of pluripotent cells from cultured somatic cells is of potential therapeutic interest, but translation to human systems would be hindered by the requirement for transgenic donors in the present iPS isolation protocol. Here we demonstrate that reprogrammed pluripotent cells can be isolated from genetically unmodified somatic donor cells solely based upon morphological criteria.

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Figure 1: Isolation and stability of iPS cells based on morphology.
Figure 2: iPS cells from genetically unmodified embryonic and adult fibroblasts.

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Acknowledgements

We thank Chris Lengner and Jacob Hanna for helpful comments on the manuscript. M.W. was supported in part by fellowships from the Human Frontiers Science Organization Program and the Ellison Foundation and R.J. by grants from the National Institutes of Health.

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Author notes

  1. Alexander Meissner and Marius Wernig: These authors contributed equally to this work.

Authors and Affiliations

  1. Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Alexander Meissner, Marius Wernig & Rudolf Jaenisch

  2. Department of Biology, Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Rudolf Jaenisch

Authors
  1. Alexander Meissner
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  2. Marius Wernig
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  3. Rudolf Jaenisch
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Contributions

A.M. and M.W. performed the experiments. A.M., M.W. and R.J. conceived the experiments and wrote the manuscript.

Corresponding author

Correspondence to Rudolf Jaenisch.

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Supplementary Figures 1 and 2; Supplementary Tables 1–3 (PDF 728 kb)

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Meissner, A., Wernig, M. & Jaenisch, R. Direct reprogramming of genetically unmodified fibroblasts into pluripotent stem cells. Nat Biotechnol 25, 1177–1181 (2007). https://doi.org/10.1038/nbt1335

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