Linking Tissue Morphology and Tissue Healing in a Cell-Fate Model

Abstract

Multicellular tissues are immensely diverse, and yet are notably similar at the microanatomical level - most tissues are organized into distinct domains with well-defined cellular compositions and precise adjacencies among themselves. Concurrently, tissues across organisms are also similar in an important functional property: the ability to heal from injury, even in organisms with poor regenerative capacities, such as mammals. Both the cellular organization within tissues and the ability of tissues to heal are outcomes of developmental processes, suggesting that the two may be intrinsically linked. In this work, we explore this connection using an agent-based model of developmental cell-fate decisions. Our model produces a rich diversity of tissue morphologies: By tuning only four parameters, which control the density of intercellular interactions and the propensity of cellular differentiation, we generate tissue structures ranging from disordered and sparse to tissues organized into dense, contiguous domains. Only tissues with large contiguous domains had the ability to heal from injuries, thus demonstrating that tissue healing is strongly coupled to tissue morphology. Moreover, model-generated tissues predominantly heal through the replacement of injured cells by cells dividing in the neighborhood, which recapitulates natural mechanisms in animals as well as plants. More generally, our modeling framework allows a systematic sampling of diverse developmental programs and reproduces healing mechanisms in organisms as phylogenetically distant as plants and animals. Our work thus points to general patterns which often are difficult to directly compare in empirical research. Despite the multiple evolutionary origins of multicellularity, the demonstrated link between tissue domain-level organization and healing capacity may represent a unifying feature of multicellular life.