Stochastic chemical kinetics of cell fate decision systems: From single cells to populations and back

Stochastic chemical kinetics is a widely used formalism for studying stochasticity of chemical reactions inside single cells. Experimental studies of reaction networks are generally performed with cells that are part of a growing population, yet the population context is rarely taken into account when models are developed. Models that neglect the population context lose their validity whenever the studied system influences traits of cells that can be selected in the population, a property that naturally arises in the complex interplay between single-cell and population dynamics of cell fate decision systems. Here, we represent such systems as absorbing continuous-time Markov chains. We show that conditioning on non-absorption allows one to derive a modified master equation that tracks the time evolution of the expected population composition within a growing population. This allows us to derive consistent population dynamics models from a specification of the single-cell process. We use this approach to classify cell fate decision systems into two types that lead to different characteristic phases in emerging population dynamics. Subsequently, we deploy the gained insights to experimentally study a recurrent problem in biology: how to link plasmid copy number fluctuations and plasmid loss events inside single cells to growth of cell populations in dynamically changing environments.

Automated summary

Stochastic chemical kinetics is a method widely used in studying the random nature of chemical reactions within individual cells, however, the influence of the population context is often ignored. In this article, a modified master equation is proposed to track the time evolution of the expected population composition within a growing population. This approach allows for the classification of cell fate decision systems and the exploration of an important problem in biology.