Matsu-Ura Toru, Nasu Atsunori, Lee Suengwon, Yoshida Naoko, Matsuura Kaoru, Yasuda Masaharu, Nakamura Kae, Hong Christian I, Tsuta Koji
Department of Pathology, Kansai Medical University, Hirakata, Osaka 573-1010, Japan.
Department of Pharmacology, Physiology, and Neurobiology, University of Cincinnati, Cincinnati, OH 45267-0576.
Proc Natl Acad Sci U S A. 2025 May 13;122(19):e2421421122. doi: 10.1073/pnas.2421421122. Epub 2025 May 8.
Circadian regulation of the cell cycle progression generates a diurnal supply of newborn cells to replace those lost in organs and tissues. In this study, we analyzed circadian time-dependent changes in cell types within the mouse tongue epithelium. Using single-cell RNA sequencing, we observed circadian time-dependent changes in the populations of stem/progenitor cells and the differentiated cells in mice tongues. Notably, we observed time-dependent changes in the type II taste cell population, which were abolished by ablation of taste bud stem cells, thereby inhibiting cell proliferation within the taste cell population. Through experiments with taste bud organoids (TBOs), we found a 24-h cell cycle period, which was disrupted by the knockdown of the core-clock gene . In TBOs, both cell divisions and apoptotic cells exhibited circadian time-dependent phenotypes. Interestingly, the time-dependent changes in cell death disappeared in the stem cell-ablated TBOs, indicating that the diurnal supply of newly born cells is essential for the rhythmic cell death phenotype. Additionally, taste tests conducted at different times of the day revealed time-dependent sensitivity changes originating from type II taste cells in mice. These findings suggest that the time-dependent changes in taste cell population are driven by circadian clock-regulated cell cycle progression and control time-dependent physiological regulation in the mouse tongue.
细胞周期进程的昼夜节律调节产生了新生细胞的每日供应，以替代器官和组织中丢失的细胞。在本研究中，我们分析了小鼠舌上皮内细胞类型的昼夜时间依赖性变化。使用单细胞RNA测序，我们观察到小鼠舌中干细胞/祖细胞群体和分化细胞的昼夜时间依赖性变化。值得注意的是，我们观察到II型味觉细胞群体的时间依赖性变化，味蕾干细胞的消融消除了这种变化，从而抑制了味觉细胞群体内的细胞增殖。通过味蕾类器官（TBO）实验，我们发现了一个24小时的细胞周期，该周期被核心时钟基因的敲低所破坏。在TBO中，细胞分裂和凋亡细胞均表现出昼夜时间依赖性表型。有趣的是，在干细胞消融的TBO中，细胞死亡的时间依赖性变化消失了，这表明新生细胞的每日供应对于节律性细胞死亡表型至关重要。此外，在一天中不同时间进行的味觉测试揭示了源自小鼠II型味觉细胞的时间依赖性敏感性变化。这些发现表明，味觉细胞群体的时间依赖性变化是由昼夜节律时钟调节的细胞周期进程驱动的，并控制着小鼠舌中的时间依赖性生理调节。
