Title: Agent-based modelling of the small intestinal crypt

Abstract: The small intestinal crypt exhibits a defined spatial organisation involving multiple cell types that undergo continuous proliferation and differentiation while migrating towards the villus. We have built a multi-scale agent-based model (ABM), with individual cells interacting in the crypt geometry, which reproduces the self-organizing stable behaviour reported for the crypt. In our ABM, spatial organization emerges from the dynamic interaction of multiple signalling pathways, which include the Wnt, Notch, BMP and RNF43/ZNRF3 pathways that orchestrate cellular fate and mechanisms of contact inhibition of proliferation as well as feedback loops that regulate the expansion of the niche and size of the crypt. Moreover, this dynamic signalling network interacts with the main cell cycle proteins, governing the progression of each cell across the division stages.