Department of Zoology

Emeritus Professor

Research area - Developmental Biology

When the nuclei of differentiated cells are transplanted to enucleated eggs, multipotential embryonic cells can be obtained. These can be made to differentiate into a range of cell types unrelated to the original cells from which the nuclei were taken. This is the basis of a cell replacement strategy by which rejuvenated cells can be derived from an adult cell. These newly-generated cells are of the same genetic constitution as the donor cell, and are therefore suitable for cell replacement therapy without the need for immunosuppression. We aim to identify the molecules and to understand the mechanisms that stabilise cell differentiation during normal development, and that therefore need to be reversed for cell rejuvenation.

Our principal method of analysis involves transplanting multiple nuclei from adult tissues such as the mouse thymus into the growing oocytes of Xenopus. Within two days, or within a few hours for the nuclei of less specialised cells, the transplanted nuclei express genes such as Oct4 and Nanog, which are diagnostic of embryo or stem cells. We analyse the reprogramming of gene expression at several levels. We have found that oocytes have a DNA demethylating activity that reverses differentiation by acting on the promoter of Oct4. We use confocal microscopy to view in real time the binding of defined proteins to somatic cell nuclei as they undergo gene reprogramming.

In related work, we find that single somatic cell nuclei transplanted to enucleated eggs often show epigenetic memory of an active gene state. This seems to be a mechanism for stabilising gene expression in a differentiation pathway, and may account for the decreasing success of nuclear transfers from more differentiated cells.

Research group - Reprogramming of gene expression by nuclear transfer

Selected publications

• Grimm, O.H. & Gurdon, J.B. (2002). Nuclear exclusion of Smad2 is a mechanism leading to loss of competence. Nature Cell Biology. 4(7): 519-522.

• Gurdon JB , Byrne JA and Simonsson S (2003) Nuclear reprogramming and stem cell creation. Proc. Natl Acad. Sci. USA 100, 11819-22.
• Byrne J.A., Simonsson S., Western P.S. & Gurdon J.B. (2003). Nuclei of adult mammalian somatic cells are directly reprogrammed to oct-4 stem cell gene expression by amphibian oocytes. Current Biology. 13(14): 1206-1213.
• Simonsson, S. & Gurdon, J. (2004). DNA demethylation is necessary for the epigenetic reprogramming o somatic cell nuclei. Nature Cell Biology. 6(10): 984-990.
• Jullien, J. & and Gurdon, J . (2005). Morphogen gradient interpretation by a regulated trafficking step during ligand-receptor transduction. Genes & Development. 19(22) : 2682-2694.
• Gurdon JB (2006) From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Ann. Rev. Cell Devel. Biol. 22, 1-22.
• Koziol MJ, Garrett N, Gurdon JB (2007) Tpt1 activates transcription of oct4 and Nanog in transplanted somatic nuclei. Curr Biol. 17, 801-807.