Nutritional regulation of cellular quiescence depth and cell cycle re-entry in Vasa2+/Piwi1+ cells in a sea anemone

Animals with lifelong growth adjust their growth rates to nutrient availability, yet the underlying cellular and molecular mechanisms remain poorly understood. Here, we studied how food supply and TOR signalling regulate the cell cycle in a multipotent, Vasa2-/Piwi1-expressing cell population in the sea anemone Nematostella vectensis . We discovered that starvation induces a reversible G ₁ /G ₀ cell cycle arrest in Vasa2+/Piwi1+ cells and that cell cycle re-entry upon refeeding is dependent on TOR signalling. In addition, the length of the refeeding stimulus after starvation determines the proportion of cells that re-enter S-phase. Remarkably, prolonged starvation delayed both refeeding-induced TOR signalling activation and S-phase re-entry. This strongly suggests that Nematostella Vasa2+/Piwi1+ cells undergo starvation-controlled quiescence deepening, previously described only in unicellular eukaryotes and mammalian cell culture. The nutritional control of quiescence and cell proliferation may thus be a fundamental, evolutionarily conserved strategy underlying the environmental regulation of indeterminate growth in animals.