Circadian clock-gated cell renewal controls time-dependent changes in taste sensitivity

Abstract Circadian regulation of the cell cycle progression produces a diurnal supply of newborn cells to replace the ones that were lost in the organs and tissues. Here we analyzed time-dependent changes in the cell types in the mouse tongue epithelium. We observed circadian regulated alternate oscillations of the stem/progenitor cell maker genes and the differentiated cell marker genes expressions in mouse tongue epithelial organoids. The cell cycle progression was regulated time-dependent manner in the tongue organoids and mice tongue. Single-cell RNA sequencing revealed time-dependent population changes of the stem/progenitor cells and the differentiated cells in mice tongues. Remarkably, we observed time-dependent type II taste cell population changes, resulting in time-dependent taste sensitivity changes. We also found the same population changes in mice intestines and uteruses, suggesting the contributions of the diurnal supply of newborn cells to the time-dependent physiological controls in the broad types of organs and tissues.