Stem cell-driven lymphatic remodeling coordinates tissue regeneration.

Publication Type Academic Article
Authors Gur-Cohen S, Yang H, Baksh S, Miao Y, Levorse J, Kataru R, Liu X, de la Cruz-Racelis J, Mehrara B, Fuchs E
Journal Science
Volume 366
Issue 6470
Pagination 1218-1225
Date Published 10/31/2019
ISSN 1095-9203
Keywords Hair Follicle, Lymphatic Vessels, Regeneration, Stem Cell Niche, Stem Cells
Abstract 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. Using a mouse model, we unravel a secretome switch in SCs that controls lymphatic behavior. Resting SCs express angiopoietin-like protein 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.
DOI 10.1126/science.aay4509
PubMed ID 31672914
PubMed Central ID PMC6996853
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