Abstract

Vasculature cross-talking with epithelial stem cells is not understood in adult skin homeostasis. Skin vasculature undergoes dramatic remodeling during adult hair cycle. Specifically, a dermal horizontal plexus transiently neighbors the hair follicle stem cell activation zone during the quiescence phase of hair homeostasis (cycle). We showed that increased density of this plexus was induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1). This increase in vasculature correlates with prolonged quiescence of hair follicle stem cells and delayed entry into the hair growth phase, suggesting an inhibitory role of dense vasculature neighboring stem cells. Suggestively, we find that skin vasculature produces BMP4, a known hair follicle stem cell quiescence-inducing factor. Our work provides a scaffold for understanding how reciprocal cross-talking between epithelial stem cells and their neighboring vasculature promotes coordinated remodeling and modulates timing of hair follicle stem cell activation for proper tissue homeostasis of adult skin.

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