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Embryonic stem cells (ES cells) are active during early development and give rise to all cell types of the organism. Nuclear reprogramming – whereby the nucleus from a differentiated somatic cell is reprogrammed to a pluripotent, embryonic-like state – was first achieved by nuclear transfer (injection of the nucleus of a differentiated cell into an undifferentiated cell, such as an oocyte) or by the fusion of somatic cells with ES cells. In 2006, Takahashi and Yamanaka reported that it is possible to reprogramme adult somatic cells to a pluripotent state by ectopically expressing four transcription factors and culturing the cells under ES cell-like conditions. The resulting cells were named 'induced pluripotent stem cells' (iPSCs).
The discovery of iPSCs has revolutionized the stem cell field, as it circumvents some of the technical challenges and ethical issues associated with the earlier nuclear reprogramming approaches. Reprogramming to iPSCs has enabled the detailed study of the intricate signalling pathways and molecular mechanisms that regulate pluripotency, cell fate specification and the stability of such states. Moreover, it has opened new therapeutic prospects, such as modelling and studying diseases, screening drugs and regenerating tissues. This specially commissioned Focus issue highlights the progress that has been made in understanding the molecular mechanisms underlying reprogramming and changes in cell fate, the properties of pluripotent stem cells (ES cells and iPSCs) and how they can be derived and maintained in culture. The articles also look at achievements, limitations and future challenges for the translation of stem cell research to the clinic.
J. B. Gurdon introduces this Focus issue by discussing the importance of the discovery of induced pluripotent stem cells 10 years ago and current challenges for the development of cell replacement therapies.
This year marks the tenth anniversary of the generation of induced pluripotent stem cells (iPSCs) by transcription factor-mediated somatic cell reprogramming. Takahashi and Yamanaka portray the path towards this ground-breaking discovery and discuss how, since then, research has focused on understanding the mechanisms underlying iPSC generation and on translating such advances to the clinic.
The ectopic expression of a defined set of transcription factors can experimentally reprogramme somatic cells into other cell types, including pluripotent cells. This method enables exploration of the molecular characteristics of pluripotency, cell specification, differentiation and cell fate stability, as well as their transcriptional and epigenetic regulation.
The use of cultured human pluripotent stem cells (PSCs) to model human diseases has revolutionized the ways in which we study monogenic, multigenic and epigenetic disorders, by overcoming some of the limitations of animal models. PSC-based disease models are generated using various strategies and can be used for the discovery of new drugs and therapies.
Recent advances in our understating of the molecular underpinnings of alternative primed- and naive-like pluripotent states in rodents and humans highlight potential functional benefits of naive pluripotency and identify key unanswered questions in this rapidly evolving field.
Advances in the derivation of pluripotent stem cells (PSCs) and their differentiation to specific cell types could have diverse clinical applications. Trounson and DeWitt provide an overview of the progress in using embryonic stem cell and induced PSC derivatives for disease treatment and discuss the potential and limitations of such approaches.
Azim Surani discusses how induced pluripotent stem cells have enabled researchers to demonstrate that it is possible to cross the germ line–soma barrier, known as the Weismann barrier.