The diverse nature of intestinal fibroblasts in development, homeostasis, and disease

Single-cell transcriptomic analyses have revealed an unexpectedly high heterogeneity in the identity and function of intestinal fibroblasts.Research from the past few years has provided compelling evidence that intestinal fibroblasts act as a niche not only for intestinal epithelial stem cells, but also for lymphatic endothelial, blood endothelial, and immune cells.Intestinal fibroblasts are a promising, yet unexplored, target for novel therapeutic interventions to combat intestinal disease. Only in recent years have we begun to appreciate the involvement of fibroblasts in intestinal development, tissue homeostasis, and disease. These insights followed the advent of single-cell transcriptomics that allowed researchers to explore the heterogeneity of intestinal fibroblasts in unprecedented detail. Since researchers often defined cell types and their associated function based on the biological process they studied, there are a plethora of partially overlapping markers for different intestinal fibroblast populations. This ambiguity complicates putting different research findings into context. Here, we provide a census on the function and identity of intestinal fibroblasts in mouse and human. We propose a simplified framework consisting of three colonic and four small intestinal fibroblast populations to aid navigating the diversity of intestinal fibroblasts.