From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation.

  title={From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation.},
  author={J. B. Gurdon},
  journal={Annual review of cell and developmental biology},
  • J. Gurdon
  • Published 9 October 2006
  • Biology
  • Annual review of cell and developmental biology
This is a personal historical account of events leading from the earliest success in vertebrate nuclear transfer to the current hope that nuclear reprogramming may facilitate cell replacement therapy. Early morphological evidence in Amphibia for the toti- or multipotentiality of some nuclei from differentiated cells first established the principle of the conservation of the genome during cell differentiation. Molecular markers show that many somatic cell nuclei are reprogrammed to an embryonic… 

Asymmetric nuclear reprogramming in somatic cell nuclear transfer?

It is suggested that a reasonable approach to balance this asymmetry in nuclear reprogramming might involve the transient expression in donor cells of chromatin remodelling proteins, which are physiologically expressed during spermatogenesis, in order to induce a male-specific chromatin organisation in the somatic cells before nuclear transfer.

Reprogramming of somatic cell identity.

By focusing on reprogramming of terminally differentiated lymphocytes, this work reviews and highlights recent insights into the molecular mechanisms and cellular events potentially underlying programming and reprograming of somatic cell identity in mammals.

Epigenetic Reprogramming Induced Pluripotency

This work has shown that the first small molecule approaches aimed at activating pluripotency genes have already been devised and that murine iPS cells have recently been derived by using non-integrative transient expression strategies of the reprogramming factors, so it is expected that human i PS cells without permanent genetic alterations will soon be generated.

Cellular Reprogramming and Fate Conversion

This chapter reviews the pioneer and recent works of cellular reprogramming and fate conversion, and also discusses the future perspective and challenges of using this technology in regenerative medicine.

Nuclear Reprogramming in Cells

Some background to this field is provided, a discussion of mechanisms and efficiency, and comments on prospects for future nuclear reprogramming research are provided.

Direct reprogramming into desired cell types by defined factors.

  • M. Ieda
  • Biology
    The Keio journal of medicine
  • 2013
The pioneering works of cellular reprogramming are reviewed and a diverse range of cell types, such as pancreatic β cells, neurons, neural progenitors, cardiomyocytes, and hepatocytes, can be directly induced from somatic cells by combinations of specific factors.

Molecular roadblocks for cellular reprogramming.

Epigenetic Reprogramming with Oocyte Molecules

An experimental approach is presented using the axolotl oocyte as a tool to broaden the understanding of the basic mechanisms of oocyte-mediated nuclear reprogramming, many of which, it is assumed, are shared by other approaches, such as transcription factor-mediated reversal to pluripotency.

Molecular mechanisms of pluripotency and reprogramming

Key transcription factors, such as Oct4, Sox2 or Nanog, have been revealed not only to regulate but also to functionally induce pluripotency, which has major impacts on the preclinical test bed of pluripotent cells.



Epigenetic memory of active gene transcription is inherited through somatic cell nuclear transfer.

  • R. K. NgJ. Gurdon
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2005
It is concluded that an epigenetic memory is established in differentiating somatic cells and applies to genes that are in a transcriptionally active state in some nuclear transplant embryos.

Reprogramming nuclei: insights from cloning, nuclear transfer and heterokaryons.

This work discusses the mechanisms involved in reprogramming nuclei after nuclear transfer and compares them with those that occur during remodeling of somaticuclei after heterokaryon formation.

DNA demethylation is necessary for the epigenetic reprogramming of somatic cell nuclei

It is found that the removal of nuclear protein accelerates the rate of reprogramming, but even more important is the demethylation of somatic cell DNA.

Nuclear Cloning and Epigenetic Reprogramming of the Genome

Survival of cloned animals to birth and beyond, despite substantial transcriptional dysregulation, is consistent with mammalian development being rather tolerant to epigenetic abnormalities, with lethality resulting only beyond a threshold of faulty gene reprogramming encompassing multiple loci.

Chromatin remodeling in nuclear cloning.

Studies involving the modification of chromatin elements such as selective uptake or release of binding proteins, covalent histone modifications including acetylation and methylation, and DNA methylation should provide significant insight into the molecular mechanisms of nuclear dedifferentiation and redifferentiation in oocyte cytoplasm.

Incomplete reactivation of Oct4-related genes in mouse embryos cloned from somatic nuclei

It is posited that cloned embryos derived from differentiated cell nuclei fail to establish a population of truly pluripotent embryonic cells because of faulty reactivation of key embryonic genes such as Oct4.

Sheep cloned by nuclear transfer from a cultured cell line

This is the first report, to the authors' knowledge, of live mammalian offspring following nuclear transfer from an established cell line, and will provide the same powerful opportunities for analysis and modification of gene function in livestock species that are available in the mouse through the use of embryonic stem cells.

Transplantation of Living Nuclei From Blastula Cells into Enucleated Frogs' Eggs.

  • R. BriggsT. J. King
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1952
The role of the nucleus in embryonic differentiation has been the subject of investigations dating back to the beginnings of experimental embryology, and the known cytogenetical mechanisms that could account for nuclear differentiation have been indicated.

Oct4 distribution and level in mouse clones: consequences for pluripotency.

The quality of GFP signals in blastocysts correlated with the ability to generate outgrowths that maintain GFP expression and the frequency of embryonic stem (ES) cell derivation, and the variations observed in Oct4 levels alone account for the majority of failures currently observed for somatic cell cloning.