Stromal control of intestinal development and the stem cell niche

Intestinal homeostasis is dependent on the continuous production of differentiated epithelial cells from a sustainable and resilient stem cell compartment. Wnt/β-catenin signaling plays a central role in this process, cooperating with R-spondins, growth factors and regulators of the TGF-β/BMP pathway to generate a specialized tissue microenvironment that regulates the intestinal stem cell niche. Recent studies revealed that many of these factors are produced in a paracrine manner by specialized cell populations that reside in the subepithelial stroma. These stromal signal-producing cells, variously called telocytes and myofibroblasts, can be identified by expression of specific genes including PdgfRa, Gli1 and FoxL1. In this review we discuss how the intestinal stem cell niche is established during development and then sustained during adult intestinal homeostasis by these stromal cell populations. The signaling stroma cells regulate intestinal stem cell development into different epithelial lineages and play an important role in the response to environmental stresses.