Challenges in describing the 'simple' sporulation-versus-quiescence differentiation decision in budding yeast

A quantitative understanding of how nutrients control the transition from proliferation to quiescence or sporulation in budding yeast has been missing. Using high-throughput experiments, we sought to parametrize the Waddington landscape for this decision, in which development is viewed as motion in a potential. The external parameters representing nutrients modify the shape of the landscape, leading to new transitions. Combining experimental data and statistical inference, we provide a model explaining these transitions. We also compare this approach with a Markov model. To test the predictive value of the landscape approach, we sought to infer the commitment points, i.e., the time after which cells will go through a developmental process, independently of reversals in environmental conditions.