Daughter cell fate choice instructed preemptively by mother cells facing nutrient limitation

Abstract

Nutrients are vital to cellular activities, yet it is largely unknown how individual cells respond to nutrient deprivation. Live imaging results show that unlike the removal of amino acids or glutamine that immediately halts cell cycle progression, glucose withdrawal does not prevent cells from completing their current cycle. Although cells that begin to experience glucose withdrawal in S phase give rise to daughter cells with an equal choice of proliferation or quiescence, those enduring such experience in G1 phase give rise to daughter cells that predominantly enter quiescence. This fate choice difference stems from p21 protein accumulated during G2/M of the latter cells. Induced degradation of p21 permits daughter cells to enter S phase but with a consequent accumulation of DNA damage. These results suggest that mother cells that begin to experience glucose limitation in G1 phase take preemptive steps toward preventing daughter cells from making a harmful choice.