Subepithelial telocytes constitute the intestinal stem cell niche

Stem cell niches provide essential signals and growth factors to sustain proliferation and self-renewal of stem cells in continuously self-renewing organs such as the intestine. We identified large mesenchymal cells expressing the winged-helix transcription factor forkhead box l1 (FOXL1) and the surface platelet derived growth factor a (PDGFRa). These cells are telocytes which have a unique cell structure with long processes that extends hundreds of micrometers . FOXL1⁺ telocytes cover the entire gut epithelium from crypt base into the villus tips and are expressing key signaling pathway molecules such as members of the Wnt, BMP, Shh, FGF and TGFb gene families in a localized fashion. Inhibition of Wnt secretion from FOXL1⁺ telocytes causes loss of proliferating cells in the crypt compartment, rapid crypt collapse, and death of the mutant mice within a few days. Thus, FOXL1⁺ telocytes constitute the intestinal stem cell niche which is absolutely required for stem cell function.