This study investigates the cellular and spatial remodeling in the gut during colitis, using MERFISH to profile gene expression in 1.35 million cells across different stages of a mouse colitis model. The researchers identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. They found a staged progression of inflammation-associated tissue neighborhoods, defined by multiple inflammation-associated fibroblasts (IAFs) with unique expression profiles, spatial localization, and cell-cell interactions. The study also explored the interactions between IAFs and other cell types, suggesting that IAFs play distinct roles in shaping neighborhood composition and function. The findings provide a framework for understanding inflammation-induced remodeling in the gut and other tissues, and suggest that similar processes may occur in human ulcerative colitis.This study investigates the cellular and spatial remodeling in the gut during colitis, using MERFISH to profile gene expression in 1.35 million cells across different stages of a mouse colitis model. The researchers identified diverse cell populations, charted their spatial organization, and revealed their polarization or recruitment in inflammation. They found a staged progression of inflammation-associated tissue neighborhoods, defined by multiple inflammation-associated fibroblasts (IAFs) with unique expression profiles, spatial localization, and cell-cell interactions. The study also explored the interactions between IAFs and other cell types, suggesting that IAFs play distinct roles in shaping neighborhood composition and function. The findings provide a framework for understanding inflammation-induced remodeling in the gut and other tissues, and suggest that similar processes may occur in human ulcerative colitis.