Histone demethylase KDM6A promotes somatic cell reprogramming by regulating PTEN and IL-6 signaling pathways

Aberrant epigenetic reprogramming is one of the major barriers of somatic cell reprogramming. Although our previous study has demonstrated that KDM6A, an H3K27me3 demethylase, can improve nuclear reprogramming efficiency, whether KDM6A also involved in IPSC generation and its role in somatic cell reprogramming remain unclear. In this study, we demonstrate that overexpression of Kdm6a can improve iPSC reprogramming efficiency in a demethylase enzymatic activity-dependent manner. In addition, Kdm6a overexpression enhanced the transcription of genes involved in cell growth and death, cellular metabolism and immune systems. Furthermore, we find that KDM6A could promote PTEN expression, further regulate p-AKT and p-mTOR levels, which may be the reason of the promotion effect, and interference of PTEN could counteracted the promotion effect of KDM6A. Besides, we find that KDM6A also can promote IL-6 expression in MEF cells and the secreted IL-6 also can improve iPSC reprogramming efficiency. Taken together our data may give insight to the relationship between epigenetic modification and somatic cell reprogramming.