Beecroft Building, Department of Physics, University of Oxford, Parks Road, Oxford, OX1 3PU
Mr Joel Hochstetter, University of Cambridge
Abstract
Epithelial tissues are in constant turnover, requiring stem cells to tightly balance cell division, differentiation and loss in order to maintain homeostasis. Squamous tissues, such as skin and oesophagus, are heterogeneous, with stem cells interspersed with their more differentiated progeny. This raises the puzzle of which feedback mechanisms govern cell fate choice to enable robust density homeostasis. To compare strategies of tissue maintenance, we develop a spatial vertex model of a 2D epithelium in which cell loss and replacement are controlled by minimal mechanical or chemical feedback. Applying this framework to clonal lineage tracing from mouse interfollicular epidermis, we infer a heterogeneous stem cell pool whose divisions are locally coordinated and biased toward asymmetric fate outcomes. To test these paradigms we turn to tissue patterning, where an empirical scaling law in the data rules out diffusible chemical signals and mechanical feedback. However, a model where stem cells regulate their fate based on local composition of cell-types can recapitulate the observed spatial patterning and emergent asymmetry without tuning, suggesting a new local paradigm of feedback in skin maintenance. Finally, in regeneration following random cell ablation, stem cells switch toward proliferation and the tissue acquires a fluid-like state. Overall, these problems show the power of minimal spatial models for uncovering the emergent rules of cell fate dynamics in epithelial tissues.