Elite and stochastic models for induced pluripotent stem cell generation

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Abstract
In the three years since Kazutoshi Takahashi and Shinya Yamanaka first demonstrated the generation of iPS (induced pluripotent stem) cells from 'normal' somatic cells using defined factors, interest in these cells has been high. Yet although they are reproducibly generated by transfection of a small number of factors, only a few per cent of transfected cells become pluripotent, and the procedure is very slow. In a review that starts with the 'pre-iPS' days, Shinya Yamanaka focuses on the mechanisms of iPS production, and on the reasons for its inefficiency and slowness. He concludes by proposing a model for direct reprogramming in which all or most cells have the potential to become pluripotent. Induced pluripotent stem cells offer unprecedented potential for disease research, drug screening, toxicology and regenerative medicine. However, the process of reprogramming is inefficient and often incomplete. Here I consider reasons for bottlenecks in induced pluripotent stem cell generation, and propose a model in which most or all cells have the potential to become pluripotent.