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Single-gene transgenic mouse strains for reprogramming adult somatic cells

Nature Methods volume 7, pages 5659 (2010) | Download Citation

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Abstract

We report transgenic mouse models in which three or four reprogramming factors are expressed from a single genomic locus using a drug-inducible transgene. Multiple somatic cell types can be directly reprogrammed to generate induced pluripotent stem cells (iPSCs) by culture in doxycycline. Because reprogramming factors are carried on a single polycistronic construct, the mice can be easily maintained, and the transgene can be easily transferred into other genetic backgrounds.

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Acknowledgements

B.W.C. thanks C. Lengner and L. Lee-Houghton for advice and assistance on somatic cell isolation techniques. We thank F. Edenhofer (University of Bonn Medical Center) for a gift of purified recombinant HTN-Cre protein, and J. Dousman and R. Flannery for mouse husbandry. J.H. is supported by a fellowship from the Helen Hay Whitney Foundation. R.J. is supported by grants from the US National Institutes of Health (5-RO1-HDO45022, 5-R37-CA084198 and 5-RO1-CA087869).

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Affiliations

  1. Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, USA.

    • Bryce W Carey
    • , Styliani Markoulaki
    • , Caroline Beard
    • , Jacob Hanna
    •  & Rudolf Jaenisch
  2. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

    • Bryce W Carey
    •  & Rudolf Jaenisch

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Contributions

B.W.C. designed and performed experiments, analyzed data and wrote the paper. S.M. performed all blastocyst injections. J.H. assisted in experiments. C.B. assisted in design of Col1a1 targeting vectors. R.J. participated in experimental design, interpreted data and assisted in writing the paper.

Competing interests

R.J. is an advisor to Stemgent and a co-founder of Fate Therapeutics.

Corresponding author

Correspondence to Rudolf Jaenisch.

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DOI

https://doi.org/10.1038/nmeth.1410

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