Investigation of the cellular reprogramming phenomenon referred to as stimulus-triggered acquisition of pluripotency (STAP).

Hitoshi Niwa

doi:10.1038/srep28003

Abstract

In January 2014, it was reported that strong external stimuli, such as a transient low-pH stressor, was capable of inducing the reprogramming of mammalian somatic cells, resulting in the generation of pluripotent cells. This cellular reprograming event was designated ‘stimulus-triggered acquisition of pluripotency’ (STAP) by the authors of these reports. However, after multiple instances of scientific misconduct in the handling and presentation of the data were brought to light, both reports were retracted. To investigate the actual scientific significance of the purported STAP phenomenon, we sought to repeat the original experiments based on the methods presented in the retracted manuscripts and other relevant information. As a result, we have concluded that the STAP phenomenon as described in the original studies is not reproducible.

Highlights

We examined the effect of hydrochloric acid (HCl) treatment on dissociated cells derived from spleen, liver and heart of 4–9-day-old mice
We investigated the properties of cell aggregates obtained by culture of liver cells transiently treated with low-pH stimulus, which was performed by the group directed by the author
We merely obtained the cell aggregates expressing the pluripotency makers as described in this report even when it was combined with the culture in medium containing fibroblast growth factor (Fgf)[2], which was not described in the original protocol but subsequently suggested by the authors

Summary

Introduction

Of cell aggregates derived from liver cells treated with ATP, 19% expressed the amount of Oct3/4 comparable to ES cells (Fig. 3c). Cell aggregates derived from low-PH treated liver cells were fixed, stained by anti-Oct3/4 antibody, and observed using confocal microscopy.

Results

Conclusion