Mathematical Modelling of Clonal Stem Cell Dynamics.

Abstract

Studying cell fate dynamics is complicated by the fact that direct in vivo observation of individual cell fate outcomesis usually not possible and only multicellular data of cell clones can be obtained. In this situation, experimental dataalone is not sufficient to validate biological models because the hypotheses and the datacannot be directly compared and thus standard statistical tests cannot be leveraged. On the other hand, mathematical modelling can bridge the scales between a hypothesis and measured data via quantitative predictions from a mathematical model. Here, we describe how to implement the rules behind a hypothesis (cell fate outcomes) one-to-one as a stochastic model, how to evaluate such a rule-based model mathematicallyvia analytical calculation or stochastic simulations of the model's Master equation, and to predict the outcomes of clonal statistics for respective hypotheses. We also illustrate two approaches to compare these predictions directly with the clonal data to assess the models.