Cai Wanting, Huang Lingci, Wu Xinwei, Zhang Haotian, Fang Zhuoning, Liu Xiao-Min
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
School of Life Science and Technology, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
Biochim Biophys Acta Mol Cell Res. 2025 Mar;1872(3):119925. doi: 10.1016/j.bbamcr.2025.119925. Epub 2025 Feb 22.
Embryonic stem cells (ESCs) exhibit remarkable pluripotency, possessing the dual abilities of self-renewal and differentiation into any cell type within the embryonic lineage. Among cultivated mouse ESCs, a subpopulation known as 2-cell-like cells (2CLCs) displays a transcriptomic signature reminiscent of the 2-cell embryonic stage, with the capacity to differentiate into both embryonic and extraembryonic tissues. These 2CLCs have served as an invaluable totipotent-like cell model for deciphering the cellular and molecular mechanisms underlying the establishment of totipotency. Accumulating evidence has indicated that a multitude of regulators including transcription factors, epigenetic modifications, and RNA regulators, exert crucial functions in the reprogramming of ESCs towards 2CLCs. In addition to 2CLCs, alternative totipotent-like cell types can be induced and maintained through the administration of single or combined chemical supplements, offering promising cell resources for regenerative medicine. In this review, we summarize the current advancements in the molecular regulations of 2CLCs and chemical manipulations of totipotent-like cells in mice, providing a foundation for understanding the regulatory networks underlying cell totipotency.
胚胎干细胞（ESCs）具有显著的多能性，具备自我更新以及分化为胚胎谱系内任何细胞类型的双重能力。在培养的小鼠胚胎干细胞中，一个被称为2细胞样细胞（2CLCs）的亚群呈现出类似于2细胞胚胎阶段的转录组特征，能够分化为胚胎组织和胚外组织。这些2细胞样细胞已成为一种极其宝贵的类全能细胞模型，用于解读全能性建立背后的细胞和分子机制。越来越多的证据表明，包括转录因子、表观遗传修饰和RNA调节因子在内的众多调节因子，在胚胎干细胞重编程为2细胞样细胞的过程中发挥着关键作用。除了2细胞样细胞外，通过施用单一或组合化学补充剂可以诱导并维持其他类全能细胞类型，为再生医学提供了有前景的细胞资源。在本综述中，我们总结了小鼠2细胞样细胞分子调控和类全能细胞化学操纵方面的当前进展，为理解细胞全能性背后的调控网络奠定基础。
