广州国家实验室闵明玮小组的一项最新研究发现双细胞样状态下的不对称分裂使胚胎干细胞恢复活力。该项研究成果发表在2026年2月3日出版的《细胞研究》上。

利用长期活细胞成像跟踪单个ESC的命运，课题组发现ESC谱系更新是通过散发进入以表达双细胞胚胎特异性标记物为特征的状态来实现的。在这种状态下，细胞经历不对称的命运分裂，将积累的DNA损伤富集成一个注定要消除的子谱系，同时产生第二个谱系，恢复到多能状态。重要的是，后者谱系显示出恢复活力的迹象，包括减少DNA损伤和提高嵌合效率。这些发现强调了不对称细胞分裂在维持ESC谱系的长期健康，抵抗单个细胞内不断增加的损伤方面的关键作用，并为研究哺乳动物细胞的细胞衰老和再生提供了一个潜在的模型。

研究人员表示，生物学中的一个基本问题是所有细胞是否都会衰老。胚胎干细胞（ESCs）是一种罕见的正常细胞，能够在体外无限传代。然而，ESC谱系不朽的机制仍未得到解决。

附：英文原文

Title: Asymmetric division in a two-cell-like state rejuvenates embryonic stem cells

Author: Wang, Xinyi, Fu, Hong, Sun, Qingyang, Huang, Boyan, Xu, Zhe, Zhai, Xuzhao, Deng, Chuncao, Peng, Laru, Zhang, Mengdan, Peng, Tianran, Gong, An, Liu, Jiasui, Zou, Zhengzhi, Pan, Guangjin, Chen, Jiekai, Wu, Guangming, Zhang, Man, Min, Mingwei

Issue&Volume: 2026-02-03

Abstract: A fundamental question in biology is whether all cells age. Embryonic stem cells (ESCs) defy the norm as rare normal cells capable of indefinite in vitro passage. However, the mechanisms underlying ESC lineage immortality remain unresolved. Using long-term live-cell imaging to follow the fates of single ESCs, we show that ESC lineage renewal is achieved through sporadic entry into a state characterized by the expression of two-cell embryo-specific markers. During this state, cells undergo asymmetric fate divisions, enriching accumulated DNA damage into one daughter lineage that is destined for elimination, while producing a second lineage that reverts to the pluripotent state. Importantly, the latter lineage exhibits signs of rejuvenation, including reduced DNA damage and enhanced chimeric efficiency. These findings underscore the crucial role of asymmetric cell division in maintaining the long-term health of the ESC lineage against mounting damage within individual cells and provide a potential model for studying cellular aging and rejuvenation in mammalian cells.

DOI: 10.1038/s41422-026-01221-z

Source: https://www.nature.com/articles/s41422-026-01221-z