CONICET | Buscador de Institutos y Recursos Humanos

Homeostasis is the regulation of the internal environment of a system in order to maintain some property in a stable, relatively constant condition. In tissue homeostasis, the relative number of cells should be maintained, therefore stem cells must balance self-renewal with differentiation, in a dynamic equilibrium. Understanding how this process is controlled in adult tissues represents a defining question in stem cell biology. The Drosophila midgut has been identified as a powerful system in which to study mechanisms that control homeostasis. Early works have established a model of tissue turnover based on the asymmetric division of intestinal stem cells. In that way, one stem cell daughter always remains pluripotent and other differentiates. Recently, an alternative scenario is proposed from the quantitative analysis of clonal fate data. It has been shown that Drosophila midgut tissue turnover involves symmetrically dividing stem cells, whose cell fate should be defined after the division. This mechanism can lead to stem-cell loss since both daughters can differentiate. What is the molecular mechanism for the symmetry breaking in stem cell daughter cells? How do the signaling pathways known to be involved in midgut tissue homeostasis interact to regulate fate decisions? One possibility is that they result in a mutual inhibition that resolves stochastically (lateral inhibition) but, is there evidence for this? And how do the spatial and temporal heterogeneities of cell distribution affect fate decision? We propose a multiscale reaction-diffusion model to address these questions. Different cell types (steam cells, committed cells and differentiated cells) and molecules (cytokines, Notch, Delta, Jak-Stat) are considered. A sparse hexagonal lattice mimics the spatial distribution of cells and allows variability and fluctuations at cell proportion. Preliminary results are presented.