https://person.zju.edu.cn/en/zhangstemcell#856074

Mouse embryonic stem cells (ESCs) show cell-to-cellheterogeneity. A small number of two-cell-like cells (2CLCs) marked byendogenous retrovirus activation emerge spontaneously. The 2CLCs are unstableand they are prone to transiting back to the pluripotent state withoutextrinsic stimulus. To understand how this bidirectional transition takesplace, we performed single-cell RNA sequencing on isolated 2CLCs that underwent2C-like state exit and re-entry, and revealed a step-by-step transitionalprocess between 2C-like and pluripotent states. Mechanistically, we found thatcell cycle played an important role in mediating these transitions byregulating assembly of the nucleolus and peri-nucleolar heterochromatin toinfluence 2C gene Dux expression. Collectively, our findings providea roadmap of the 2C-like state entry and exit in ESCs and also a causal role ofthe cell cycle in promoting these transitions.