A mathematical model of cell fate selection on a dynamic tissue

TL;DR

This paper introduces a multiscale mathematical model linking cell motility and intercellular signalling to understand cell fate decisions in dynamic tissues, highlighting the importance of signalling affinity and turnover rates for tissue health.

Contribution

It presents a novel multicellular, multiscale model connecting cell movement and signalling to explain tissue homeostasis and cell differentiation.

Findings

Cell signalling affinity influences differentiation ability.

High cell turnover rates can lead to unhealthy tissues.

Model supports the importance of finely tuned differentiation processes.

Abstract

Multicellular tissues are the building blocks of many biological systems and organs. These tissues are not static, but dynamically change over time. Even if the overall structure remains the same there is a turnover of cells within the tissue. This dynamic homeostasis is maintained by numerous governing mechanisms which are finely tuned in such a way that the tissue remains in a homeostatic state, even across large timescales. Some of these governing mechanisms include cell motion, and cell fate selection through inter cellular signalling. However, it is not yet clear how to link these two processes, or how they may affect one another across the tissue. In this paper, we present a multicellular, multiscale model, which brings together the two phenomena of cell motility, and inter cellular signalling, to describe cell fate selection on a dynamic tissue. We find that the affinity for cellular signalling to occur greatly influences a cells ability to differentiate. We also find that our results support claims that cell differentiation is a finely tuned process within dynamic tissues at homeostasis, with excessive cell turnover rates leading to unhealthy (undifferentiated and unpatterned) tissues.