Tox4 modulates cell fate reprogramming

Reprogramming to induced pluripotency induces the switch of somatic cell identity to induced pluripotent stem cells (iPSCs). However, the mediators and mechanisms of reprogramming remain largely unclear. To elucidate the mediators and mechanisms of reprogramming, we used a siRNA-mediated knockdown approach for selected candidate genes during the conversion of somatic cells into iPSCs. We identified as a novel factor that modulates cell fate through an assay that determined the efficiency of iPSC reprogramming. We found that is needed early in reprogramming to efficiently generate early reprogramming intermediates, irrespective of the reprogramming conditions used. enables proper exogenous reprogramming factor expression, and the closing and opening of putative somatic and pluripotency enhancers early during reprogramming, respectively. We show that the TOX4 protein assembles into a high molecular form. Moreover, is also required for the efficient conversion of fibroblasts towards the neuronal fate, suggesting a broader role of in modulating cell fate. Our study reveals as a novel transcriptional modulator of cell fate that mediates reprogramming from the somatic state to the pluripotent and neuronal fate.This article has an associated First Person interview with the first author of the paper.