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Nature 385, 810 - 813 (27 February 1997); doi:10.1038/385810a0

Viable offspring derived from fetal and adult mammalian cells

I. Wilmut, A. E. Schnieke*, J. McWhir, A. J. Kind* & K. H. S. Campbell

Roslin Institute (Edinburgh), Roslin, Midlothian EH25 9PS, UK
*PPL Therapeutics, Roslin, Midlothian EH25 9PP, UK

Fertilization of mammalian eggs is followed by successive cell divisions and progressive differentiation, first into the early embryo and subsequently into all of the cell types that make up the adult animal. Transfer of a single nucleus at a specific stage of development, to an enucleated unfertilized egg, provided an opportunity to investigate whether cellular differentiation to that stage involved irreversible genetic modification. The first offspring to develop from a differentiated cell were born after nuclear transfer from an embryo-derived cell line that had been induced to become quiescent1. Using the same procedure, we now report the birth of live lambs from three new cell populations established from adult mammary gland, fetus and embryo. The fact that a lamb was derived from an adult cell confirms that differentiation of that cell did not involve the irreversible modification of genetic material required for development to term. The birth of lambs from differentiated fetal and adult cells also reinforces previous speculation1,2 that by inducing donor cells to become quiescent it will be possible to obtain normal development from a wide variety of differentiated cells.

  1. Campbell, K. H. S., McWhir, J., Ritchie, W. A. & Wilmut, I. Sheep cloned by nuclear transfer from a cultured cell line. Nature 380, 64−66 (1996). | Article | PubMed | ISI | ChemPort |
  2. Solter, D. Lambing by nuclear transfer. Nature 380, 24−25 (1996). | Article | PubMed | ISI | ChemPort |
  3. Gurdon, J. B., Laskey, R. A. & Reeves, O. R. The developmental capacity of nuclei transplanted from keratinized skin cells of adult frogs. J. Embryol. Exp. Morph. 34, 93−112 (1975). | PubMed | ISI | ChemPort |
  4. Quinlivan, T. D., Martin, C. A., Taylor, W. B. & Cairney, I. M. Pre- and perinatal mortality in those ewes that conceived to one service. J. Reprod. Fert. 11, 379−390 (1966). | ChemPort |
  5. Walker, S. K., Heard, T. M. & Seamark, R. F. In vitro culture of sheep embryos without co-culture: successes and perspectives. Therio 37, 111−126 (1992).
  6. Nash, M. L., Hungerford, L. L., Nash, T. G. & Zinn, G. M. Risk factors for perinatal and postnatal mortality in lambs. Vet. Rec. 139, 64−67 (1996). | PubMed | ChemPort |
  7. Bradford, G. E., Hart, R., Quirke, J. F. & Land, R. B. Genetic control of the duration of gestation in sheep. J. Reprod. Fert. 30, 459−463 (1972). | ChemPort |
  8. Walton, A. & Hammond, J. The maternal effects on growth and conformation in Shire horse-Shetland pony crosses. Proc. R. Soc. B 125, 311−335 (1938).
  9. Campbell, K. H. S., Loi, P., Otaegui, P. J. & Wilmut, I. Cell cycle co-ordination in embryo cloning by nuclear transfer. Rev. Reprod. 1, 40−46 (1996). | Article | PubMed | ChemPort |
  10. Cheong, H.-T., Takahashi, Y. & Kanagawa, H. Birth of mice after transplantation of early-cell-cycle-stage embryonic nuclei into enucleated oocytes. Biol. Reprod. 48, 958−963 (1993). | PubMed | ISI | ChemPort |
  11. Prather, R. S. et al. Nuclear transplantation in the bovine embryo. Assessment of donor nuclei and recipient oocyte. Biol. Reprod. 37, 859−866 (1987). | PubMed | ISI | ChemPort |
  12. McGrath, J. & Solter, D. Inability of mouse blastomere nuclei transferred to enucleated zygotes to support development in vitro. Science 226, 1317−1318 (1984). | PubMed | ISI | ChemPort |
  13. Robl, J. M. et al. Nuclear transplantation in bovine embryos. J. Anim. Sci. 64, 642−647 (1987). | PubMed | ChemPort |
  14. Campbell, K. H. S., Ritchie, W. A. & Wilmut, I. Nuclear-cytoplasmic interactions during the first cell cycle of nuclear transfer reconstructed bovine embryos: Implications for deoxyribonucleic acid replication and development. Biol. Reprod. 49, 933−942 (1993). | PubMed | ISI | ChemPort |
  15. Barnes, F. L. et al. Influence of recipient oocyte cell cycle stage on DNA synthesis, nuclear envelope breakdown, chromosome constitution, and development in nuclear transplant bovine embryos. Mol. Reprod. Dev. 36, 33−41 (1993). | Article | PubMed | ChemPort |
  16. Kwon, O. Y. & Kono, T. Production of identical sextuplet mice by transferring metaphase nuclei from 4-cell embryos. J. Reprod. Fert. Abst. Ser. 17, 30 (1996).
  17. Gurdon, J. B. The control of gene expression in animal development (Oxford University Press, Oxford, 1974).
  18. Finch, L. M. B. et al. Primary culture of ovine mammary epithelial cells. Biochem. Soc. Trans. 24, 369S (1996). | PubMed | ChemPort |
  19. Whitten, W. K. & Biggers, J. D. Complete development in vitro of the preimplantation stages of the mouse in a simple chemically defined medium. J. Reprod. Fertil. 17, 399−401 (1968). | PubMed | ChemPort |
  20. Gardner, D. K., Lane, M., Spitzer, A. & Batt, P. A. Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells. Amino acids, vitamins, and culturing embryos in groups stimulate development. Biol. Reprod. 50, 390−400 (1994). | PubMed | ChemPort |
  21. Breslow, N. E. & Clayton, D. G. Approximate inference in generalized linear mixed models. J. Am. Stat. Assoc. 88, 9−25 (1993).
  22. Buchanan, F. C., Littlejohn, R. P., Galloway, S. M. & Crawford, A. L. Microsatellites and associated repetitive elements in the sheep genome. Mammal. Gen. 4, 258−264 (1993). | ChemPort |

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