RETRACTED ARTICLE: Stimulus-triggered fate conversion of somatic cells into pluripotency

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. One of two papers describing a reprogramming phenomenon called stimulus-triggered acquisition of pluripotency (STAP) -- in STAP, lineage-committed adult somatic cells are reprogrammed to pluripotency by transient exposure to low-pH treatment, and extensive analysis of the molecular features and developmental potential of STAP cells indicates that they represent a unique state of pluripotency. A new way to induce pluripotency The fates of the somatic cells that form the bulk of the mammalian body are thought to be largely determined by the time the cellular differentiation processes of development have been completed. Reprogramming in response to environmental stress has been observed in plants but not so far in mammalian cells. Now two manuscripts by Haruko Obokata and colleagues describe an unexpected reprogramming phenomenon, which the authors call stimulus-triggered acquisition of pluripotency (STAP). In STAP, mouse somatic cells such as CD45.sup.+ haematopoietic cells are reprogrammed to pluripotency by transient exposure to low pH. Extensive analysis of the molecular features and developmental potential of STAP cells suggests that they represent a unique state of pluripotency -- and provide an alternative source of pluripotent cells to the use of transcription factors, as has become routine for induced pluripotent stem cell production.
Author(s): Haruko Obokata [sup.1] [sup.2] [sup.3], Teruhiko Wakayama [sup.3] [sup.8], Yoshiki Sasai [sup.4], Koji Kojima [sup.1], Martin P. Vacanti [sup.1] [sup.5], Hitoshi Niwa [sup.6], Masayuki Yamato [sup.7], Charles A. Vacanti [...]