Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

References

  1. Takahashi, K. & Yamanaka, S. Cell 126, 663–676 (2006).

    Article  CAS  Google Scholar 

  2. Okita, K., Ichisaka, T. & Yamanaka, S. Nature 448, 313–317 (2007).

    Article  CAS  Google Scholar 

  3. Wernig, M. et al. Nature 448, 318–324 (2007).

    Article  CAS  Google Scholar 

  4. Maherali, N. et al. Cell Stem Cell 1, 55–70 (2007).

    Article  CAS  Google Scholar 

  5. Hanna, J. et al. Cell 133, 250–264 (2008).

    Article  CAS  Google Scholar 

  6. Wernig, M. et al. Nat. Biotechnol. 26, 916–924 (2008).

    Article  CAS  Google Scholar 

  7. Maherali, N. et al. Cell Stem Cell 3, 340–345 (2008).

    Article  CAS  Google Scholar 

  8. Hockemeyer, D. et al. Cell Stem Cell 3, 346–353 (2008).

    Article  CAS  Google Scholar 

  9. Markoulaki, S. et al. Nat. Biotechnol. 27, 169–171 (2009).

    Article  CAS  Google Scholar 

  10. Hochedlinger, K., Yamada, Y., Beard, C. & Jaenisch, R. Cell 121, 465–477 (2005).

    Article  CAS  Google Scholar 

  11. Beard, C., Hochedlinger, K., Plath, K., Wutz, A. & Jaenisch, R. Genesis 44, 23–28 (2006).

    Article  CAS  Google Scholar 

  12. Carey, B.W. et al. Proc. Natl. Acad. Sci. USA 106, 157–162 (2009).

    Article  CAS  Google Scholar 

  13. Soldner, F. et al. Cell 136, 964–977 (2009).

    Article  CAS  Google Scholar 

  14. Kaji, K. et al. Nature 458, 771–775 (2009).

    Article  CAS  Google Scholar 

  15. Woltjen, K. et al. Nature 458, 766–770 (2009).

    Article  CAS  Google Scholar 

  16. Yusa, K. et al. Nat. Methods 6, 363–369 (2009).

    Article  CAS  Google Scholar 

Download references

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).

Author information

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
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Styliani Markoulaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caroline Beard
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacob Hanna
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rudolf Jaenisch
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Ethics declarations

Competing interests

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

Supplementary information

Supplementary Text and Figures

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

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing