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.

Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells

Nature volume 336, pages 684–687 (1988)Cite this article

Abstract

Embryonic stem (ES) cells, the totipotent outgrowths of bias-tocysts1,2, can be cultured and manipulated in vitro and then returned to the embryonic environment where they develop normally and can contribute to all cell lineages3–9. Maintenance of the stem-cell phenotype in vitro requires the presence of a feeder layer of fibroblasts1,2,10 or of a soluble factor, differentiation inhibitory activity (DIA) produced by a number of sources5,11,12; in the absence of DIA the ES cells differentiate into a wide variety of cell types. We recently noted several similarities between partially purified DIA and a haemopoietic regulator, myeloid leukaemia inhibitory factor (LIF), a molecule which induces differentiation in Ml myeloid leukaemic cells and which we have recently purified, cloned and characterized13–18. We demonstrate here that purified, recombinant LIF can substitute for DIA in the maintenance of totipotent ES cell lines that retain the potential to form chimaeric mice.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Evans, M. J. & Kaufman, M. H. Nature 292, 154–156 (1981).

    ADS  CAS  Article  Google Scholar 

  2. Martin, G. R. Proc. natn. Acad. Sci. U.S.A. 78, 7634–7638 (1981).

    ADS  CAS  Article  Google Scholar 

  3. Bradley, A., Evans, M., Kaufman, M. H. & Robertson, E. Nature 309, 255–256 (1984).

    ADS  CAS  Article  Google Scholar 

  4. Robertson, E. J., Bradley, A., Kuehn, M. & Evans, M. Nature 323, 445–448 (1986).

    ADS  CAS  Article  Google Scholar 

  5. Hooper, M., Hardy, K., Handyside, A., Hunter, S. & Monk, M. Nature 326, 292–295 (1987).

    ADS  CAS  Article  Google Scholar 

  6. Kuehn, M. R., Bradley, A., Robertson, E. J. & Evans, M. J. Nature 326, 295–298 (1987).

    ADS  CAS  Article  Google Scholar 

  7. Williams, R. L., Courtneidge, S. A. & Wagner, E. F. Cell 52, 121–131 (1988).

    CAS  Article  Google Scholar 

  8. Stewart, C. L., Vanek, M. & Wagner, E. F. EMBO J. 4, 383–388 (1985).

    Article  Google Scholar 

  9. Gossler, A., Doetschmann, T., Korn, R., Serfling, E. & Kemler, R. Proc. natn. Acad. Sci. U.S.A. 83, 9065–9069 (1986).

    ADS  CAS  Article  Google Scholar 

  10. Martin, G. R. & Evans, M. J. Proc. natn. Acad. Sci. U.S.A. 72, 1441–1445 (1975).

    ADS  CAS  Article  Google Scholar 

  11. Smith, A. G. & Hooper, M. L. Devl Biol. 121, 1–9 (1987).

    CAS  Article  Google Scholar 

  12. Koopman, P. & Cotton, R. G. H. Exptl Cell Res. 154, 233–242 (1984).

    CAS  Article  Google Scholar 

  13. Gearing, D. P. et al. EMBO J. 6, 3995–4002 (1987).

    CAS  Article  Google Scholar 

  14. Gough, N. M. et al. Proc. natn. Acad. Sci. U.S.A. 85, 2623–2627 (1988).

    ADS  CAS  Article  Google Scholar 

  15. Hilton, D. J., Nicola, N. A., Gough, N. M. & Metcalf, D. J. biol. Chem. 263, 9238–9443 (1988).

    CAS  PubMed  Google Scholar 

  16. Metcalf, D., Hilton, D. J. & Nicola, N. A. Leukaemia 2, 216–221 (1988).

    CAS  Google Scholar 

  17. Hilton, D. J., Nicola, N. A. & Metcalf, D. Analyt. Biochem. 173, 359–367 (1988).

    CAS  Article  Google Scholar 

  18. Simpson, R. J. et al. Eur. J. Biochem. 175, 541–547 (1988).

    CAS  Article  Google Scholar 

  19. Hilton, D. J., Nicola, N. A. & Metcalf, D. Proc. natn. Acad. Sci. U.S.A. 85, 5971–5975 (1988).

    ADS  CAS  Article  Google Scholar 

  20. Wagner, E. F., Keller, G., Gilboa, E., Rüther, U. & Stewart, C. Cold Spring Harb. Symp. quant. Biol. 50, 691–700 (1985).

    CAS  Article  Google Scholar 

  21. Jakob, J., Bonn, T., Gaillard, J., Nicolas, J. F. & Jacob, F. Ann. Microbiol. (Inst. Pasteur) 124B, 269–282 (1973).

    Google Scholar 

  22. Rudnicki, M. A. & McBurney, M. W. in Teratocarcinomas and Embryonic Stem Cells, a Practical Approach (ed. E. J. Robertson) 19–49 (IRL, Oxford, 1987).

    Google Scholar 

  23. Doetschman, T., Eistetter, H., Katz, M., Schmidt, W. & Kemler, R. J. Embryol. exp. Morphol. 87, 27–45 (1985).

    CAS  PubMed  Google Scholar 

  24. Dewey, M. J., Martin, D. W., Martin, G. R. & Mintz, B. Proc. natn. Acad. Sci. U.S.A. 74, 5564–5568 (1977).

    ADS  CAS  Article  Google Scholar 

  25. Kemler, R. in Progress in Developmental Biology Band 26 (ed. Sauer, H. W.) 175 (Fisher, Stuttgart, 1980).

    Google Scholar 

  26. Thomas, K. R. & Capecchi, M. R. Cell 51, 503–512 (1987).

    CAS  Article  Google Scholar 

  27. Doetschman, T. et al. Nature 330, 576–577 (1987).

    ADS  CAS  Article  Google Scholar 

  28. Munson, P. J. & Rodbard, D. Analyt. Biochem. 107, 220–237 (1980).

    CAS  Article  Google Scholar 

  29. Nicola, N. A. & Metcalf, D. J. cell. Physiol. 124, 313–321 (1985).

    CAS  Article  Google Scholar 

  30. Smith, D. B. & Johnson, K. S. Gene 67, 31–40 (1988).

    CAS  Article  Google Scholar 

  31. Smith, A. G. et al. Nature 336, 688–690 (1988).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Author notes

  1. Colin L. Stewart

    Present address: Roche Institute for Molecular Biology, Nutley, New Jersey

  2. Erwin F. Wagner

    Present address: Institute for Molecular Pathology, Dr Bohr-Gasse 7, 1030, Vienna, Austria

Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstrasse 1, 6900, Heidelberg, FRG

    R. Lindsay Williams, Shirley Pease, Colin L. Stewart & Erwin F. Wagner

  2. The Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Post Office, Victoria, 3050, Australia

    Douglas J. Hilton, Tracy A. Willson, David P. Gearing, Donald Metcalf, Nicos A. Nicola & Nicholas M. Gough

  3. Roche Institute for Molecular Biology, Nutley, New Jersey

    Erwin F. Wagner

  4. Institute for Molecular Pathology, Dr Bohr-Gasse 7, 1030, Vienna, Austria

    Colin L. Stewart

Authors
  1. R. Lindsay Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Douglas J. Hilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shirley Pease
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tracy A. Willson
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Colin L. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David P. Gearing
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Erwin F. Wagner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Donald Metcalf
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nicos A. Nicola
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nicholas M. Gough
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Williams, R., Hilton, D., Pease, S. et al. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 336, 684–687 (1988). https://doi.org/10.1038/336684a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/336684a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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