The use of embryonic stem cells to study hematopoietic development in mammals

  • Michael V. Wiles
  • Britt M. Johansson
Conference paper


To study the process of mesoderm and subsequent hematopoietic cell development in mammals, we used embryonic stem (ES) cells in vitro differentiation. In fetal bovine serum containing medium, ES cell differentiation appears to be refractive to most exogenously added growth factors. Therefore to avoid the masking effects of serum we developed a serum-free, chemically defined medium (CDM). In CDM, ES cells grown as aggregates (known as embryoid bodies (EBs)), differentiate to neuroectoderm. If however activin A is added to CDM, both neuroectoderm and mesoderm develop. If bone morphogenetic protein 4 (BMP-4) is present in CDM, a process resembling primitive streak formation (at the molecular level) is induced, including the development of hematopoietic cells. These data combined with other reports strongly suggest that BMP-4 is intimately involved in mesoderm formation and possibly early hematopoietic development.


Embryonic Stem Cell Leukemia Inhibitory Factor Definitive Endoderm chemicaIly Define Medium Embryonic Stem Cell Differentiation 
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  1. 1.
    A. L. Medvinsky, N. L. Samoylina, A. M. Muller, E. A. Dzierzak, Nature 364, 64–7 (1993).PubMedCrossRefGoogle Scholar
  2. 2.
    D. S. Kessler, D. A. Melton, Science 266, 596–604 (1994).PubMedCrossRefGoogle Scholar
  3. 3.
    A. J. van den Eijnden-Van Raaij, et al., Nature 345, 732–4 (1990).CrossRefGoogle Scholar
  4. 4.
    J. C. Smith, B. M. Price, N. K. Van, D. Huylebroeck, Nature 345, 729–31 (1990).PubMedCrossRefGoogle Scholar
  5. 5.
    C. M. Jones, K. M. Lyons, B. L. Hogan, Development 111, 531–42 (1991).PubMedGoogle Scholar
  6. 6.
    M. Köster, et al., Mech Dev 33, 191–9 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    R. W. Padgett, J. M. Wozney, W. M. Gelbart, Proc Natl Acad Sci U S A 90, 2905–9 (1993).PubMedCrossRefGoogle Scholar
  8. 8.
    M. J. Evans, M. H. Kaufman, Nature 292, 154–6 (1981).PubMedCrossRefGoogle Scholar
  9. 9.
    G. R. Martin, Proc Nall Acad Sci U S A 78, 7634–8 (1981).Google Scholar
  10. 10.
    R. L. Williams, et al., Nature 336, 684–7 (1988).PubMedCrossRefGoogle Scholar
  11. 11.
    A. Bradley, M. Evans, M. H. Kaufman, E. Robertson, Nature 309, 255–6 (1984).PubMedCrossRefGoogle Scholar
  12. 12.
    A. M. Wobus, H. Holzhausen, P. Jakel, J. Schoneich, Exp Cell Res 152, 212–9 Issn: 0014–4827 (1984).Google Scholar
  13. 13.
    T. C. Doetschman, H. Eistetter, M. Katz, W. Schmidt, R. Kemler, J Embryol Exp Morphol 87, 27–45 (1985).PubMedGoogle Scholar
  14. 14.
    M. V. Wiles, G. Keller, Development 111, 259–67 (1991).PubMedGoogle Scholar
  15. 15.
    G. Keller, M. Kennedy, T. Papayannopoulou, M. V. Wiles, Molecular And Cellular Biology 13, 473–486 (1993).PubMedGoogle Scholar
  16. 16.
    B. M. Johansson, M. V. Wiles, Mol Cell Biol15, 141–51 (1995).Google Scholar
  17. 17.
    K. Manova, B. V. Paynton, R. F. Bachvarova, Mech Dev 36, 141–52 (1992).PubMedCrossRefGoogle Scholar
  18. 18.
    G. Winnier, M. Blessing, P. A. Labosky, B. L. M. Hogan, Genes & Development 9, 2105–2116 (1995).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1996

Authors and Affiliations

  • Michael V. Wiles
    • 1
  • Britt M. Johansson
    • 1
  1. 1.Basel Institute for ImmunologyBaselSwitzerland

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