Stimulus-triggered fate conversion of

Abstract

Here we report a unique cellular reprogramming phenomenon, called stimulus-triggered acquisition of pluripotency {(STAP),} which requires neither nuclear transfer nor the introduction of transcription factors. In {STAP,} strong external stimuli such as a transient {low-pH} stressor reprogrammed mammalian somatic cells, resulting in the generation of pluripotent cells. Through real-time imaging of {STAP} cells derived from purified lymphocytes, as well as gene rearrangement analysis, we found that committed somatic cells give rise to {STAP} cells by reprogramming rather than selection. {STAP} cells showed a substantial decrease in {DNA} methylation in the regulatory regions of pluripotency marker genes. Blastocyst injection showed that {STAP} cells efficiently contribute to chimaeric embryos and to offspring via germline transmission. We also demonstrate the derivation of robustly expandable pluripotent cell lines from {STAP} cells. Thus, our findings indicate that epigenetic fate determination of mammalian cells can be markedly converted in a context-dependent manner by strong environmental cues.