Stem cell-driven lymphatic remodeling coordinates tissue regeneration.

Tissues rely on stem cells (SCs) for homeostasis and wound-repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC-niche components. In skin, lymphatics form intimate networks around hair follicle (HF) SCs. When HFs regenerate, lymphatic:SC connections become dynamic. We unravel a secretome switch within SCs that controls lymphatic behavior. Resting SCs express Angiopoietin-like 7 ( Angptl7) , promoting lymphatic drainage. Activated SCs switch to Angptl4 , triggering transient lymphatic dissociation and reduced drainage. When lymphatics are perturbed or the secretome switch is disrupted, HFs cycle precociously and tissue regeneration becomes asynchronous. In unearthing lymphatic capillaries as a critical SC-niche element, we have learned how SCs coordinate their activity across a tissue.