BRG1 enhances porcine iPSC pluripotency through WNT/β-catenin and autophagy pathways.

Brahma-related gene 1 (BRG1) enhances the pluripotency of embryonic and adult stem cells, however, its effect on induced pluripotent stem cell (iPSC) pluripotency has not been reported. The aim of this study was to investigate the effect of BRG1 on porcine iPSC pluripotency and its mechanisms. The effect of BRG1 on porcine iPSC pluripotency was explored by positive and negative control it. The mechanism was investigated by regulating the WNT/β-catenin signaling pathway and autophagy flux. The results showed that inhibition of BRG1 decreased pluripotency-related gene expression in porcine iPSCs; while its overexpression had the opposite effect, the expression of WNT/β-catenin signaling pathway- and autophagy-related genes was significantly up-regulated (P < 0.05) in the BRG1 overexpressed group when compared to the control group. Inhibited pluripotency-related gene or protein expression, decreased autophagy flux, and increased mitochondrial length and mitochondrial membrane potential (MMP) were observed when porcine iPSCs were treated with the WNT/β-catenin signaling pathway inhibitor IWR-1. Forced BRG1 expression restored porcine iPSC pluripotency, increased autophagy flux, shortened mitochondria, and reduced MMP. Lastly, Compound C was used to activate porcine iPSC autophagy, and it was found that the expression of BRG1 and β-catenin increased, and pluripotency-related gene and protein expression was up-regulated; these effects were reversed when the BRG1 inhibitor PFI-3 and IWR-1 were added. These results suggested that BRG1 enhanced the pluripotency of porcine iPSCs through WNT/β-catenin and autophagy pathways. • BRG1 facilitates the maintenance of porcine iPSCs pluripotency. • BRG1 rescues the loss of pluripotency in porcine iPSCs caused by WNT/β-catenin signaling pathway inhibitor IWR-1. • Inhibition of BRG1 reverses autophagy activation and pluripotency caused by autophagy activator Compound C. [ABSTRACT FROM AUTHOR]