Telocytes are an important source of Wnts essential for hair follicle regeneration

Stem cells reside within niches determined by local cues which maintain its function in tissue homeostasis support. It is well established that the Wnt/b-catenin signaling is essential in the control of a variety of stem cells, including neural, mammary, intestine and skin. Although the need for active Wnt-signaling in the stem-cell compartment has long been known, the cellular identity of the stem-cell niche, which provides the molecular Wnt ligands essential to induce proliferation, is still controversial. In the intestine, we recently identified a subepithelial network of unique mesenchymal cells, called telocytes, as an important stem cell niche component essential for regeneration. Telocytes express the transcription factor Forkhead Box l1 (Foxl1) and in this study, we investigated whether Foxl1 labels telocytes in the skin and whether telocytes are an important hair follicle stem cell niche component. Using careful tissue fixation conditions, whole mount tissue clearing and detailed histology of two independent Foxl1 driven mouse models, we revealed a comprehensive 3D network of inter- and sub-follicular telocytes along the entire hair follicle concentric layers accompanying stem, progenitor and differentiated cells. We specifically ablated telocytes or Wnt signaling emanating from telocytes at the onset of hair follicle growth and demonstrated that Foxl1 telocytes are a critical source of Wnt proteins essential for hair follicle regeneration and thus constitute the hair follicle stem cell niche.