Integration of Multiple Metabolic Signals Determines Cell Fate Prior to Commitment

Abstract

Cell-fate decisions are central to the survival and development of both uni- and multicellular organisms. It remains unclear when and to what degree cells can decide on future fates prior to commitment. This uncertainty stems from experimental and theoretical limitations in measuring and integrating multiple signals at the single-cell level during a decision process. Here, we combine six-color live-cell imaging with the Bayesian method of statistical evidence to study the meiosis/quiescence decision in budding yeast. Integration of multiple upstream metabolic signals predicts individual cell fates with high probability well before commitment. Cells "decide" their fates before birth, well before the activation of pathways characteristic of downstream cell fates. This decision, which remains stable through several cell cycles, occurs when multiple metabolic parameters simultaneously cross cell-fate-specific thresholds. Taken together, our results show that cells can decide their future fates long before commitment mechanisms are activated.

Keywords: Bayesian analysis; cell size; cellular decision-making; deterministic; meiosis; quantitative imaging; quiescence; sporulation; statistical evidence; stochastic.