Xiaotao Dong, Rong Guo, Tianrong Ji, Jie Zhang, Jun Xu, Yaoyi Li, Yingliang Sheng, Yuxiang Wang, Ke Fang, Yulin Wen, Bei Liu, Gongcheng Hu, Hongkui Deng, Hongjie Yao
Nucleic Acids Research, gkac230, https://doi.org/10.1093/nar/gkac230
Extended pluripotent stem cells (EPSCs), which can form both embryonic and extraembryonic lineages, have important application prospect in regenerative medicine. However, the epigenetic regulation in EPSCs remains unclear. In this study, we demonstrated that EPSCs have the uniquely epigenetic signature compared with ESCs and discovered that Yin Yang-1 (YY1) acting as a key regulator could safeguard EPSC extended pluripotency by controlling epigenetic crosstalk among DNA methylation, histone modification and high-order chromatin structure. Moreover, YY1 is required for the in vitro derivation of extraembryonic endoderm (XEN)-like cells from EPSCs. Together, this study highlights the importance of a YY1-DNA methylation-chromatin loops-histone modification axis in regulating EPSC identity and development potentials.