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Single-gene transgenic mouse strains for reprogramming adult somatic cells

Nature Methods volume 7, pages 56–59 (2010)Cite this article

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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Figure 1: Reprogramming somatic cells from transgenic Col1a1 4F2A mice.
Figure 2: Reprogramming somatic cells from transgenic Col1a1 3F2A mice.
Figure 3: Cre recombinase–excisable Col1a1 4F2A transgenic ESCs.

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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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Authors and 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

Authors
  1. Bryce W Carey
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  2. Styliani Markoulaki
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  3. Caroline Beard
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  4. Jacob Hanna
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  5. 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.

Corresponding author

Correspondence to Rudolf Jaenisch.

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Competing interests

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

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Supplementary Figures 1–6 and Supplementary Tables 1–5 (PDF 5348 kb)

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Carey, B., Markoulaki, S., Beard, C. et al. Single-gene transgenic mouse strains for reprogramming adult somatic cells. Nat Methods 7, 56–59 (2010). https://doi.org/10.1038/nmeth.1410

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