Progress | Published:

Somatic cell nuclear transfer


Cloning by nuclear transfer from adult somatic cells is a remarkable demonstration of developmental plasticity. When a nucleus is placed in oocyte cytoplasm, the changes in chromatin structure that govern differentiation can be reversed, and the nucleus can be made to control development to term.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Wilmut, I. & Peterson, L. A. Somatic cell nuclear transfer (cloning) efficiency [online] 〈〉 (2002).

  2. 2

    Young, L. E. & Fairburn, H. R. Improving the safety of embryo technologies: possible role of genomic imprinting. Theriogenology 53, 627–648 (2000)

  3. 3

    Hill, J. R. et al. Evidence for placental abnormality as the major cause of mortality in first-trimester somatic cell cloned bovine fetuses. Biol. Reprod. 63, 1787–1794 (2000)

  4. 4

    Hill, J. R. et al. Clinical and pathologic features of cloned transgenic calves and fetuses (13 case studies). Theriogenology 51, 1451–1465 (1999)

  5. 5

    Heyman, Y. et al. Frequency and occurrence of late-gestation losses from cattle cloned embryos. Biol. Reprod. 66, 6–13 (2002)

  6. 6

    Hasler, J. F. et al. Production, freezing and transfer of bovine IVF embryos and subsequent calving results. Theriogenology 43, 141–152 (1995)

  7. 7

    Wells, D. et al. Proc. 32nd Ann. Conf. Soc. Reprod. Biol. Abstract No. 25 (2001)

  8. 8

    Tanaka, S. et al. Placentomegaly in cloned mouse concepti caused by expansion of the spongiotrophoblast layer. Biol. Reprod. 65, 1813–1821 (2001)

  9. 9

    Tamashiro, K. L. et al. Cloned mice have an obese phenotype not transmitted to their offspring. Nature Med. 8, 262–267 (2002)

  10. 10

    Ogonuki, N. et al. Early death of mice cloned from somatic cells. Nature Genet. 30, 253–254 (2002)

  11. 11

    Lanza, R. P. et al. Cloned cattle can be healthy and normal. Science 294, 1893–1894 (2001)

  12. 12

    Campbell, K. H., Loi, P., Otaegui, P. J. & Wilmut, I. Cell cycle co-ordination in embryo cloning by nuclear transfer. Rev. Reprod. 1, 40–46 (1996)

  13. 13

    Ono, Y., Shimozawa, N., Ito, M. & Kono, T. Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer. Biol. Reprod. 64, 44–50 (2001)

  14. 14

    Wakayama, T. & Yanagimachi, R. Effect of cytokinesis inhibitors, DMSO and the timing of oocyte activation on mouse cloning using cumulus cell nuclei. Reproduction 122, 49–60 (2001)

  15. 15

    Chesne, P. et al. Cloned rabbits produced by nuclear transfer from adult somatic cells. Nature Biotechnol. 20, 366–369 (2002)

  16. 16

    Wilmut, I., Schnieke, A. E., McWhir, J., Kind, A. J. & Campbell, K. H. S. Viable offspring derived from fetal and adult mammalian cells. Nature 385, 810–813 (1997)

  17. 17

    Kasinathan, P., Knott, J. G., Wang, Z., Jerry, D. J. & Robl, J. M. Production of calves from G1 fibroblasts. Nature Biotechnol. 19, 1176–1178 (2001)

  18. 18

    Wells, D. et al. Proc. Curr. Status Perspec. Cloning Stud. 73 (National Institute of Agrobiological Sciences, Tsukuba, Japan, 2001)

  19. 19

    Zhou, Q., Jouneau, A., Brochard, V., Adenot, P. & Renard, J. P. Developmental potential of mouse embryos reconstructed from metaphase embryonic stem cell nuclei. Biol. Reprod. 65, 412–419 (2001)

  20. 20

    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)

  21. 21

    Wakayama, T., Perry, A. C. F., Zuccotti, M., Johnson, K. R. & Yanagimachi, R. Full-term development of mice from enucleated oocytes injected with cumulus cell nuclei. Nature 394, 369–374 (1998)

  22. 22

    Kubota, C. et al. Six cloned calves produced from adult fibroblast cells after long-term culture. Proc. Natl Acad. Sci. USA 97, 990–995 (2000)

  23. 23

    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)

  24. 24

    Thompson, E. M. Chromatin structure and gene expression in the preimplantation mammalian embryo. Reprod. Nutr. Dev. 36, 619–635 (1996)

  25. 25

    Yamazaki, Y. et al. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer. Proc. Natl Acad. Sci. USA 98, 14022–14026 (2001)

  26. 26

    Hochedlinger, K. & Jaenisch, R. Monoclonal mice generated by nuclear transfer from mature B and T cells. Nature 415, 967–969 (2002)

  27. 27

    Wakayama, T. & Yanagimachi, R. Mouse cloning with nucleus donor cells of different age and type. Mol. Reprod. Dev. 58, 376–383 (2001)

  28. 28

    Young, L. E. et al. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nature Genet. 27, 153–154 (2001)

  29. 29

    Humpherys, D. et al. Epigenetic instability in ES cells and cloned mice. Science 293, 95–97 (2001)

  30. 30

    Inoue, K. et al. Faithful expression of imprinted genes in cloned mice. Science 295, 297 (2002)

  31. 31

    Daniels, R., Hall, V. & Trounson, A. O. Analysis of gene transcription in bovine nuclear transfer embryos reconstructed with granulose cell nuclei. Biol. Reprod. 63, 1034–1040 (2000)

  32. 32

    Rideout, W. M., Eggan, K. & Jaenisch, R. Nuclear cloning and epigentic reprogramming of the genome. Science 293, 1093–1098 (2001)

  33. 33

    Misteli, T. Protein dynamics: implications for nuclear architecture and gene expression. Science 291, 843–847 (2001)

  34. 34

    Clarke, H. J., McLay, D. W. & Mohamed, O. A. Linker histone transitions during mammalian oogenesis and embryogenesis. Dev. Genet. 22, 17–30 (1998)

  35. 35

    Bordignon, V., Clarke, H. J. & Smith, L. C. Factors controlling the loss of immunoreactive somatic histone H1 from blastomere nuclei in oocyte cytoplasm: a potential marker of nuclear reprogramming. Dev. Biol. 233, 192–203 (2001)

  36. 36

    Nakao, M. Epigenetics: interaction of DNA methylation and chromatin. Gene 278, 25–31 (2001)

  37. 37

    Kikyo, N., Wade, P. A., Guschin, D., Ge, H. & Wolffe, A. P. Active remodeling of somatic nuclei in egg cytoplasm by the nucleosomal ATPase ISWI. Science 289, 2360–2362 (2000)

  38. 38

    Robertson, K. D. & Wolffe, A. P. DNA methylation in health and disease. Nature Rev. Genet. 1, 11–19 (2000)

  39. 39

    Fairburn, H. R., Young, L. E. & Hendrich, B. D. Epigenetic reprogramming: how now, cloned cow. Curr. Biol. 12, R68–R70 (2002)

Download references


We each acknowledge discussions with colleagues during the development of these ideas and are grateful for funding from the governments, charities and commercial agencies acknowledged in our research papers.

Author information

Correspondence to I. Wilmut.

Rights and permissions

Reprints and Permissions

About this article

Further reading

Figure 1: A comparison of survival to term of bovine embryos produced either by in vitro fertilization or nuclear transfer from embryos, fetal or adult fibroblasts.
Figure 2: 5-Methyl cytosine immunostaining of pronuclear DNA in mouse and sheep zygotes.


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.