A novel population of subepithelial platelet-derived growth factor receptor α-positive cells in the mouse and human colon

Abstract

Recently platelet-derived growth factor-α-positive cells (PDGFRα(+) cells), previously called "fibroblast-like" cells, have been described in the muscle layers of the gastrointestinal tract. These cells form networks and are involved in purinergic motor neurotransduction. Examination of colon from mice with enhanced green fluorescent protein (eGFP) driven from the endogenous Pdgfra (PDGFRα-eGFP mice) revealed a unique population of PDGFRα(+) cells in the mucosal layer of colon. We investigated the phenotype and potential role of these cells, which have not been characterized previously. Expression of PDGFRα and several additional proteins was surveyed in human and murine colonic mucosae by immunolabeling; PDGFRα(+) cells in colonic mucosa were isolated from PDGFRα-eGFP mice, and the gene expression profile was analyzed by quantitative polymerase chain reaction. We found for the first time that PDGFRα was expressed in subepithelial cells (subepithelial PDGFRα(+) cells) forming a pericryptal sheath from the base to the tip of crypts. These cells were in close proximity to the basolateral surface of epithelial cells and distinct from subepithelial myofibroblasts, which were identified by expression of α-smooth muscle actin and smooth muscle myosin. PDGFRα(+) cells also lay in close proximity to varicose processes of nerve fibers. Mouse subepithelial PDGFRα(+) cells expressed Toll-like receptor genes, purinergic receptor genes, 5-hydroxytryptamine (5-HT) 4 receptor gene, and hedgehog signaling genes. Subepithelial PDGFRα(+) cells occupy an important niche in the lamina propria and may function in transduction of sensory and immune signals and in the maintenance of mucosal homeostasis.