The role of replication-removal spatial correlations and cellular replicative lifespan in corneal epithelium homeostasis

Abstract

AbstractHomeostasis in adult tissues relies on the replication dynamics of stem cells, their progenitors and the spatial balance between them. This spatial and kinetic coordination is crucial to the successful maintenance of tissue size and its replenishment with new cells. However, our understanding of the role of cellular replicative lifespan and spatial correlation between cells in shaping tissue integrity is still lacking. We developed a mathematical model for the stochastic spatial dynamics that underlie the rejuvenation of corneal epithelium. Our model takes into account different spatial correlations between cell replication and cell removal. We derive the tradeoffs between replicative lifespan, spatial correlation length, and tissue rejuvenation dynamics. We determine the conditions that allow homeostasis and are consistent with biological timescales, pattern formation, and mutants phenotypes. Our results can be extended to any cellular system in which spatial homeostasis is maintained through cell replication.