Emergence of metabolic heterogeneity in cell populations: lessons from budding yeast

Abstract

Complex microbial communities are commonly found in nature. Interactions between cells within multispecies communities can provide both benefits and disadvantages, for example, due to division of labor or competition for resources, respectively. However, even genetically identical cell populations commonly exhibit such phenomena, with apparent phenotypic differences amongst cells. We use examples from budding yeast to show how such phenotypic heterogeneity may emerge in groups of isogenic cells. We include examples of phenotypic heterogeneity in cell communities restricted by space, as well as cells in well-mixed communities where heterogeneity exhibits temporal oscillations. In particular, we focus on metabolic constraints that can trigger phenotypic heterogeneity. We provide a theoretical and experimental framework to understand the underlying basis of such phenomena, driven by inherent bistabilities driving oscillatory behavior, as well as resource production and sharing.