Telocytes are a critical source of Wnts essential for hair follicle regeneration

In multiple tissues, stem cell proliferation driving tissue regeneration is dependent on Wnt/β-catenin signaling, but the identity of the niche cells providing the Wnt proteins is not resolved. Here, we show that telocytes, unique interstitial cells that harbor long cytoplasmic extensions, are obligatory Wnt-producing niche cells in the hair follicle. Employing two independent mouse models we reveal a continuous network of interconnected telocytes that envelopes stem cells and their progeny along the path of differentiation. Telocytes compartmentalize in space and time the production of mRNA molecules that encode important signaling factors, for localized phase-dependent signaling. Ablation of either dermal telocytes, or the Wnt signals emanating from them, abrogates hair follicle regeneration, demonstrating that telocytes constitute a critical component of the hair follicle stem cell niche. We propose that telocyte production of Wnt is a universal theme in adult stem cell biology and tissue regeneration.