Global quantitative understanding of non-equilibrium cell fate decision-making in response to pheromone

Cell-cycle arrest and polarized growth are commonly used to characterize the response of yeast to pheromone. However, the quantitative decision-making processes underlying time-dependent changes in cell fate remain unclear. In this study, we conducted single-cell level experiments to observe multidimensional responses, uncovering diverse fates of yeast cells. Multiple states are revealed, along with the kinetic switching rates and pathways among them, giving rise to a quantitative landscape of mating response. To quantify the experimentally observed cell fates, we developed a theoretical framework based on non-equilibrium landscape and flux theory. Additionally, we performed stochastic simulations of biochemical reactions to elucidate signal transduction and cell growth. Notably, our experimental findings have provided the first global quantitative evidence of the real-time synchronization between intracellular signaling, physiological growth, and morphological functions. These results validate the proposed underlying mechanism governing the emergence of multiple cell fate states. This study introduces an emerging mechanistic approach to understand non-equilibrium cell fate decision-making in response to pheromone.