Research Article

Stem cell–driven lymphatic remodeling coordinates tissue regeneration

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Science  06 Dec 2019:
Vol. 366, Issue 6470, pp. 1218-1225
DOI: 10.1126/science.aay4509

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Stem cells reshape a lymphatic niche

Adult stem cells can both self-renew and regenerate new tissue upon demand. They reside in microenvironments (niches) that balance these decisions to avoid tissue overgrowth, cancer, and aging. Using murine skin as a model, Gur-Cohen et al. uncovered a lymphatic network of capillaries associated with the stem cell niche of hair follicles (see the Perspective by Harvey). Stem cells reshaped their lymphatic environment by switching their secretome to coordinate lymphatic-niche association. During tissue regeneration, a dynamic change in epithelial-lymphatic communication remodeled this association, synchronizing stem cell and niche behavior.

Science, this issue p. 1218; see also p. 1193


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.

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