Novel insights into cell cycle regulation of cell fate determination
- 32 Downloads
The stem/progenitor cell has long been regarded as a central cell type in development, homeostasis, and regeneration, largely owing to its robust self-renewal and multilineage differentiation abilities. The balance between self-renewal and stem/progenitor cell differentiation requires the coordinated regulation of cell cycle progression and cell fate determination. Extensive studies have demonstrated that cell cycle states determine cell fates, because cells in different cell cycle states are characterized by distinct molecular features and functional outputs. Recent advances in high-resolution epigenome profiling, single-cell transcriptomics, and cell cycle reporter systems have provided novel insights into the cell cycle regulation of cell fate determination. Here, we review recent advances in cell cycle-dependent cell fate determination and functional heterogeneity, and the application of cell cycle manipulation for cell fate conversion. These findings will provide insight into our understanding of cell cycle regulation of cell fate determination in this field, and may facilitate its potential application in translational medicine.
Key wordsCell cycle Cell fate Heterogeneity Fate conversion Stem/progenitor cell
长期以来,干/祖细胞由于其具备的自我更新和多 谱系分化能力,因而被视为生物体发育、稳态和 再生过程中的一类重要细胞类型。干/祖细胞自我 更新和多谱系分化之间的平衡是由细胞周期进 程和细胞命运决定之间的协同调控来完成的。大 量研究表明细胞周期状态可以决定细胞的命运, 体现在处于不同细胞周期状态的细胞具有不同 的分子特征和功能。目前,随着高分辨率的表观 基因组学、单细胞转录组学和细胞周期实时标记 系统的开发,我们对细胞周期如何调控细胞命运 有了新的认识。本文总结了细胞周期调控细胞命 运决定和功能异质性的分子机制,以及通过操纵 细胞周期进而影响细胞命运转变的研究进展。这 些发现将加深我们对细胞周期调控细胞命运决 定机制的理解,同时也能促进其在转化医学中的 潜在应用。
关键词细胞周期 细胞命运 异质性 命运转变 干/祖细胞
The study was also supported by the State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
- Kar S, Wang MF, Yao W, et al., 2006. PM-20, a novel inhibitor of Cdc25A, induces extracellular signal-regulated kinase 1/2 phosphorylation and inhibits hepatocellular carcinoma growth in vitro and in vivo. Mol Cancer Ther, 5(6): 1511–1519. https://doi.org/10.1158/1535-7163.Mct-05-0485 Google Scholar
- Lu CJ, Fan XY, Guo YF, et al., 2019. Single-cell analyses identify distinct and intermediate states of zebrafish pancreatic islet development. J Mol Cell Biol, mjy064. https://doi.org/10.1093/jmcb/mjy064