Induced pluripotency decoded

The investigators of the Project Grandiose consortium report their effort to characterize the protein, DNA and RNA changes associated with transcription-factor-mediated reprogramming to pluripotency in two papers in this issue of Nature and three papers published concurrently in Nature Communications. In the first of the Nature papers, Andras Nagy and colleagues report that when mouse embryonic fibroblasts are made to express high levels of reprogramming factors, they reach an alternative pluripotent stable state termed F-class (from the 'fuzzy' appearance of the cell colonies in culture). The second paper presents an extensive analysis of transcriptomic, epigenomic and proteomic datasets describing the routes to pluripotency. They describe the existence of several paths towards induced pluripotency, characterized by distinct epigenetic events. In a News & Views article, Juan Carlos Izpisua Belmonte discusses the results from all five papers in the context of other recent work and speculates on the likelihood of alternative states of pluripotency.