A stochastic model of homeostasis: The roles of noise and nuclear positioning in deciding cell fate

We study a population-based cellular model that starts from a single stem cell that divides stochastically to give rise to either daughter stem cells or differentiated daughter cells. There are three main components in the model: nucleus position, the underlying gene-regulatory network, and stochastic segregation of transcription factors in the daughter cells. The proportion of self-renewal and differentiated cell lines as a function of the nucleus position which in turn decides the plane of cleavage is studied. Both nuclear position and noise play an important role in determining the stem cell genealogies. We have observed both long and short genealogies in model simulation, and these compare well with experimental results from neuroblast and B-cell division. Symmetric divisions are observed in apical nuclei, while asymmetric division occurs when the nucleus is toward the base. In this model, the number of clones decreases over time, although the average clone size increases.