RETRACTED ARTICLE: Stimulus-triggered fate conversion of somatic cells into pluripotency

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.

The Inherent Drawbacks of the Pressure to Publish in Health Sciences: Good or Bad Science

“…More recently in January 2014, Haruko Obokata, a young researcher in Japan published in Nature , showed stem cells can now be made quickly just by dipping blood cells into acid 25, 26 . On June 2014, Obokata agreed to retract both the papers and 2 months later Obokata’s mentor and co-author, Yoshiki Sasai, committed suicide by hanging.…”

Results of an attempt to reproduce the STAP phenomenon

“…Experiments were performed using a transgenic mouse line harboring GFP under an Oct4 promoter ( Ohbo et al , 2003); the line is the same as that used in the previous studies ( Obokata et al , 2014a; Obokata et al , 2014b). The mouse line has been maintained in C57BL/6 background in a homozygous state.…”

“…This discovery raised the possibility that cellular reprogramming may also be induced by activating endogenous pluripotency genes under certain conditions. In two reports published in Nature by Obokata et al (2014a); Obokata et al (2014b), the authors claimed to have observed how “external stimuli such as a transient low-pH stressor reprogram somatic cells into pluripotent cells,” which they referred to as the STAP phenomenon; subsequently, however, after multiple problems were found with the handling and presentation of the data in a pattern indicative of research misconduct, both papers were retracted.…”

“…There were no significant differences in the data generated in the preliminary and formal experiments, and all are included together in this report. The experiments were conducted in a new setting, not in the laboratory that Obokata had used for the previous studies described in the retracted Nature publications ( Obokata et al , 2014a; Obokata et al , 2014b). All reagents, materials, instruments, and experimental spaces were freshly furnished.…”

“…Other members of the team conducted chimeric, FACS, RT-PCR and immunohistochemical analyses of the cell aggregates. In this report, I refer to the studies reported in the papers retracted ( Obokata et al , 2014a; Obokata et al , 2014b) as "the previous studies" for the sake of brevity. I also refer to the technical tips published by several authors of the original articles for details of the experimental procedure ( Obokata et al , 2014c).…”