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The birth and adult development of “Dolly” the sheep, the first mammal produced by transfer of a terminally differentiated cell nucleus into an egg, provided unequivocal evidence of nuclear equivalence among somatic cells. This ground-breaking experiment challenged a long-standing dogma of irreversible cellular differentiation that prevailed for over a century and enabled the development of methodologies for reversal of differentiation of somatic cells, also known as nuclear reprogramming. Thanks to this new paradigm, novel alternatives for regenerative medicine in humans, improved animal breeding in domestic animals and approaches to species conservation through reproductive methodologies have emerged. Combined with the incorporation of new tools for genetic modification, these novel techniques promise to i) transform and accelerate our understanding of genetic diseases and the development of targeted therapies through creation of tailored animal models, ii) provide safe animal cells, tissues and organs for xenotransplantation, iii) contribute to the preservation of endangered species, and iv) improve global food security whilst reducing the environmental impact of animal production. This review discusses recent advances that build on the conceptual legacy of nuclear transfer and - when combined with gene editing - will have transformative potential for medicine, biodiversity and sustainable agriculture. We conclude that the transformative potential of these technologies depends on further fundamental and translational research directed at improving the efficiency and safety of these methods.

Recent scientific achievements in cell and developmental biology have provided unprecedented opportunities for advances in biomedical research. The demonstration that fully differentiated cells can reverse their gene expression profile to that of a pluripotent cell, and the successful derivation and culture of human embryonic stem cells (ESCs) have fuelled hopes for applications in regenerative medicine. These advances have been put to public scrutiny raising legal, moral and ethical issues which have resulted in different levels of acceptance. Ethical issues concerning the use of cloned human embryos for the derivation of stem cells have stimulated the search for alternative methods for reversing differentiated cells into multi/pluripotent cells. In this article, we will review the present state of these reprogramming technologies and discuss their relative success. We also overview reprogramming events after somatic cell nuclear transfer (SCNT), as they may further instructex ovostrategies for cellular manipulation.

In this issue, we introduce what we hope will become a series of highly topical and, in some instances, controversial debate articles. Our idea is to promote constructive discussion of arguments both ‘for’ and ‘against’ particular research concepts, and so foster and direct future research endeavors that will shed light into new and exciting areas of reproductive biology. The first Debate in this series could not be more appropriate, as it deals with the highly controversial topic of differentiation of human embryonic stem cells (hESC) into trophoblast cells. The contributors, led by R Michael Roberts and Roger Pedersen, are the leading researchers in this field. In this issue they present a detailed account of the evidence both for and against this biological concept (Roberts et al. 2014). There is great interest in both the scientific and medical communities in determining whether hESC can differentiate into a functional trophoblast, as this may lead to the development of in vitro models of placentation. In turn, this could be used to improve our understanding of placental dysfunctions such as pre-eclampsia (Ezashi et al. 2012). However, it is