Stimulus-triggered fate conversion of somatic cells into pluripotency
A surprising new way to generate stem cells has been presented by Obokata et al. The authors found that low-pH stress applied to cells from various tissues, when grown in a medium supplemented with leukaemia inhibtory factor (LIF) and B27, causes the formation of pluripotent cells which are named "stimulus-triggered acquisition of pluripotency" (STAP) cells. Other stress stimuli, such as physical damage, also induced the formation of STAP cells, but low-pH was the most efficient. They worked with Oct4-gfp transgene mouse lymphocytes, which allowed the monitoring of the expression levels of the pluripotency marker Oct4, according to the amount of observed fluorescence in the cells. They found extensive demethylation in Oct4 and another pluripotency gene Nanog, in STAP cells, suggesting substantial epigenetic modification during physical stress.
When STAP cells were grafted into mice they formed teratomas, which are non-malignant encapsulated tumors with tissue or organ components resembling normal derivatives of more than one germ layer. Once parental STAP cells were formed, if they were grown in a medium used to grow embryonic stem (ES) cells, STAP stem cells were formed. These have unlimited proliferative potential and behave very much like ES cells. After blastocyst injection, STAP stem cells efficiently contributed to chimeric mice, and in differentiation culture generated: ectodermal, mesodermal and endodermal derivatives in vitro, including beating cardiac tissue. The precise mechanism of how these somatic cells gained pluripotency after physical stress is still a mystery, but raises many questions such as: how is this reprogramming mechanism normally repressed? and what epigenetic mechanism unites such disparate physical stresses to cause this response?
This article was retracted on 03 July 2014