GSE138815
Histone demethylase KDM6A promotes somatic cell reprogramming by epigenetically regulate PTEN and IL-6 signal pathway [RNA-seq]
Aberrant epigenetic reprogramming is one of the major barriers for somatic cell reprogramming. Although our previous study has demonstrated that KDM6A, a H3K27me3 demethylase, could improve nuclear reprogramming efficiency, but its role in somatic cell reprogramming and the mechanism remain unclear. In this study, we demonstrated that overexpression of Kdm6a could improve iPSC reprogramming efficiency in a demethylase enzymatic activity-dependent manner. And Kdm6a overexpression changed the gene expression profile and metabolic pattern through erasing the repressive H3K27me3 in fibroblast. Besides, we proved that KDM6A could promote IL-6 expression in MEF cells and the secreted IL-6 also could improve iPSC reprogramming efficiency. Furthermore, we found that KDM6A could promote PTEN expression, further regulate p-AKT and p-mTOR levels, which favor the reprogramming, and interference of PTEN could counteracted the promotion effect of KDM6A. Taken together, our data revealed that KDM6A could promote iPSC reprogramming efficiency by accelerate the change of gene expression profile and metabolic pattern in a demethylation-activity-dependent manner, which may give insight to the relationship between epigenetic modification and somatic cell reprogramming. Overall design: 48 hrs after infection or 72h post DOX was added, the total RNA of 4F2A MEFs was harvested by using TRIzol reagent (Invitrogen), each group was prepared with three parallel replicates. Then, all the samples were sent to BGI Corporation (China) for further RNA-seq analysis via BGISEQ-500 sequencer. The GO and KEGG pathway analyses were performed based on the KEGG database on the Dr. Tom network platform of BGI (http://report.bgi.com).