Joel Hochastetter, University of Cambridge

Mechanochemical feedback model for squamous tissue maintanence

Throughout adult life epithelial tissues are constantly turned over, demanding a delicate between cell loss and replenishment through division and differentiation of stem cells. Using a 2D Voronoi model with division and death, we propose a potential feedback mechanisms for squamous tissue maintenance based competition for biochemical fate determinants, which can robustly converge to a homeostatic steady state from different initial conditions and enables control of the fractions of different cell-types. We study the key phenomenology in terms of clonal dynamics, patterning and phase behaviour at homeostasis. In non-homeostatic conditions, such as mutant clone competition and recovery to homeostasis, we identify distinct predictions between this model and local mechanical feedback models. Through applying our model to in vivo long-term time-lapse experiments, we find a stem/progenitor hierarchy with specific temporal correlations of cell fate are needed to explain the fate behaviour of mouse skin homeostasis. As of yet our results cannot distinguish our chemical feedback mechanism from a local mechanical feedback. However, integrating spatiotemporal data from mutant and regeneration experiments may pave the way forward.