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Chemical reprogramming of Caenorhabditis elegans germ cell fate

Abstract

Small molecules can control cell fate in vivo and may allow directed induction of desired cell types, providing an attractive alternative to transplant-based approaches in regenerative medicine. We have chemically induced functional oocytes in Caenorhabditis elegans adults that otherwise produced only sperm. These findings suggest that chemical approaches to therapeutic cell reprogramming may be feasible and provide a powerful platform for analyzing molecular mechanisms of in vivo cell reprogramming.

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Figure 1: Small molecule–mediated reprogramming of sperm/oocyte fate.
Figure 2: Small molecule–induced oocytes are functional.

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References

  1. Gurdon, J.B. & Melton, D.A. Science 322, 1811–1815 (2008).

    Article  CAS  PubMed  Google Scholar 

  2. Zhou, Q., Brown, J., Kanarek, A., Rajagopal, J. & Melton, D.A. Nature 455, 627–632 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Xu, Y., Shi, Y. & Ding, S. Nature 453, 338–344 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. North, T.E. et al. Nature 447, 1007–1011 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Castaigne, S. et al. Blood 76, 1704–1709 (1990).

    CAS  PubMed  Google Scholar 

  6. Kimble, J. & Crittenden, S.L. Annu. Rev. Cell Dev. Biol. 23, 405–433 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Ellis, R. & Schedl, T. in WormBook (ed. The C. elegans Research Community) doi/10.1895/wormbook.1.82.1 (4 April 2006). http://www.wormbook.org>

  8. Barton, M.K., Schedl, T.B. & Kimble, J. Genetics 115, 107–119 (1987).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lee, M.-H. et al. Genetics 177, 2039–2062 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sundaram, M.V. in WormBook (ed. The C. elegans Research Community) doi/10.1895/wormbook.1.80.1 (11 February 2006). http://www.wormbook.org>

  11. Berset, T., Fröhli Hoier, E., Battu, G., Canevascini, S. & Hajnal, A. Science 291, 1055–1058 (2001).

    Article  CAS  PubMed  Google Scholar 

  12. Bachorik, J.L. & Kimble, J. Proc. Natl. Acad. Sci. USA 102, 10893–10897 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Albertson, D.G., Rose, A.M. & Villeneuve, A.M. Chromosome organization, mitosis, and meiosis. in C. elegans II (eds. Riddle, D.L., Blumenthal, T., Meyer, B.J. & Priess, J.R.) 47–78 (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, USA, 1997).

  14. Favata, M.F. et al. J. Biol. Chem. 273, 18623–18632 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Duncia, J.V. et al. Bioorg. Med. Chem. Lett. 8, 2839–2844 (1998).

    Article  CAS  PubMed  Google Scholar 

  16. Gumienny, T.L., Lambie, E., Hartwieg, E., Horvitz, H.R. & Hengartner, M.O. Development 126, 1011–1022 (1999).

    CAS  PubMed  Google Scholar 

  17. Church, D.L., Guan, K.-L. & Lambie, E.J. Development 121, 2525–2535 (1995).

    CAS  PubMed  Google Scholar 

  18. Barrett, S.D. et al. Bioorg. Med. Chem. Lett. 18, 6501–6504 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Alessi, D.R., Cuenda, A., Cohen, P., Dudley, D.T. & Saltiel, A.R. J. Biol. Chem. 270, 27489–27494 (1995).

    Article  CAS  PubMed  Google Scholar 

  20. Dudley, D.T., Pang, L., Decker, S.J., Bridges, A.J. & Saltiel, A.R. Proc. Natl. Acad. Sci. USA 92, 7686–7689 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lee, M.-H. et al. PLoS Genet. 3, e233 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  22. Subramaniam, K. & Seydoux, G. Curr. Biol. 13, 134–139 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Hajnal, A. & Berset, T. EMBO J. 21, 4317–4326 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tenen, D.G. Nat. Rev. Cancer 3, 89–101 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. McLachlan, R.I., Rajpert-De Meyts, E., Hoei-Hansen, C.E., de Kretser, D.M. & Skakkebaek, N.E. Hum. Reprod. 22, 2–16 (2007).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank S. Ward (University of Arizona) and B. Grant (Rutgers University) for providing reagents. We are grateful to L. Vanderploeg, A. Steinberg and A. Helsley-Marchbanks for help preparing the figures and manuscript. We thank the Kimble lab members for helpful discussions. This work was supported by US National Institutes of Health grant RO1 GM069454. J.K. is an investigator with the Howard Hughes Medical Institute.

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Contributions

C.T.M. and M.-H.L. performed the experiments. C.T.M., M.-H.L. and J.K. analyzed the results. C.T.M. and J.K. wrote the manuscript.

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Correspondence to Judith Kimble.

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Supplementary Methods, Supplementary Figures 1–4 and Supplementary Table 1 (PDF 5811 kb)

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Morgan, C., Lee, MH. & Kimble, J. Chemical reprogramming of Caenorhabditis elegans germ cell fate. Nat Chem Biol 6, 102–104 (2010). https://doi.org/10.1038/nchembio.282

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