Gall2023 - Agent-based model of the intestinal epithelium

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.

小肠隐窝（small intestinal crypt）具备明确的空间组织结构，包含多种细胞类型；这些细胞在向肠绒毛（villus）迁移的过程中持续开展增殖与分化活动。
我们构建了一款多尺度智能体模型（agent-based model，ABM），该模型中单个细胞于隐窝几何结构内相互作用，可复现已有文献报道的隐窝自组织稳定行为。
在本智能体模型中，空间组织结构源自多条信号通路的动态交互作用，涵盖Wnt、Notch、BMP及RNF43/ZNRF3通路；这些通路不仅调控细胞命运与增殖接触抑制机制，还通过反馈环路调节干细胞龛（niche）的扩张规模与隐窝尺寸。
此外，该动态信号网络还与核心细胞周期蛋白发生相互作用，调控每个细胞在分裂各阶段的进程。