Stromal Niche Signals That Orchestrate Intestinal Regeneration

Stromal cell populations have a central role in providing signals that support the maintenance, differentiation, and function of the intestinal epithelium. The behavior and fate of epithelial cells is directed by the spatial organization of stromal cells that either sustain stem and progenitor cell identity or drive differentiation. A combination of single-cell analyses, mouse models, and organoid coculture assays have provided insight into the diversity of signals delivered by stromal cells. Signaling gradients are established and fine-tuned by the expression of signaling agonists and antagonists along the crypt-villus axis. On epithelial injury, there are disruptions to the abundance and organization of stromal populations. There are also distinct changes in the signals originating from these cells that impact remodeling of the epithelium. How these signals coordinate to mediate epithelial repair or sustain tissue injury in inflammatory bowel diseases is beginning to emerge. Understanding of these processes may lead to opportunities to target stromal cell populations as a strategy to modify disease states.