Stem cells possess the unique capacity to self-renew and to activate one or several differentiation programs. Although cell replacement therapy is still far from being realized, recent research has been driven by the prospects that stem cells represent for regenerative medicine.

Since John Gurdon's discovery that the developmental clock of a differentiated nucleus could be reset to its pluripotent state, stem cells scientists have attempted to reprogramme somatic cells in a controlled manner. This was finally achieved by Shinya Yamanaka and colleagues in 2006 using a defined set of transcription factors. Since then, the pace of stem cell research has accelerated in the reprogramming field and in other areas essential for future clinical applications, including understanding how stem cell activity maintains organ homeostasis in mature tissues. To celebrate the blooming of this field, we are pleased to present Reviews and Perspective articles written by leading experts focusing on recent advances in stem cell research.

Sean Wu and Konrad Hochedlinger review recent progress and future challenges for researchers using patient-specific pluripotent cells obtained through reprogramming approaches. Studying these cells provides insights into the cellular and molecular basis of a range of diseases and offers opportunities for developing novel therapeutic tools. Several technical advances have increased our current understanding of stem cell physiology. The ability to maintain embryonic stem cells in vitro has meant that a systems approach can be applied to analyse the signalling and transcriptional networks responsible for pluripotency, and Huck-Hui Ng and Azim Surani examine the recent findings illustrating the dynamic nature of pluripotency. Understanding how the regenerative capacity of adult tissues is tapped to maintain homeostasis and activate repair is crucial for future therapeutic applications. A first step in this direction consists of identifying stem cells in their natural environment. Elaine Fuchs and Valerie Horsley consider advances in lineage-tracing technologies that have allowed the identification and functional characterization of stem cells within mammalian adult tissues. Finally, Thomas Rando and Leanne Jones discuss findings from both invertebrate and mammalian models that have led to an enhanced appreciation of age-related changes in stem cell function, including decreased self-renewal capacity and impaired differentiation, which ultimately result in reduced tissue maintenance and repair.

We hope that this Focus issue captures the excitement of stem cell research while also illustrating the numerous challenges to be met before these fundamental findings can be translated into clinical applications.