Abstract

Skin and other epithelial (surface-coating) tissues look static but are in fact very dynamic: old cells continuously die and are replaced by new cells that emerge from the division of stem cells and subsequent differentiation. This represents a stationary non-equilibrium state of the tissue cell population. The question is how the proliferation and differentiation of stem cells — the stem cell fate — is accurately balanced to maintain this state, since otherwise tissue degeneration or aberrant growth may emerge, the latter leading to tumours.

Here I will present different model strategies of cell fate dynamics in tissues, and will show, by comparison with biological in-vivo cell lineage data, that stem cell fate decisions are determined by a high degree of stochasticity. The relevant stochastic cell fate models are related to classical stochastic processes and to statistical physics lattice (spin) models (Ising and voter model). It turns out that a novel paradigm, involving some degree of reversibility in differentiation (“spin flips”), leads to a robust viable mechanism of stochastic tissue maintenance which is consistent with experimental results.