Stem cell-driven lymphatic remodeling coordinates tissue regeneration

Science. 2019 Dec 6;366(6470):1218-1225. doi: 10.1126/science.aay4509. Epub 2019 Oct 31.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-Like Protein 4 / metabolism
  • Angiopoietin-Like Protein 7
  • Angiopoietin-like Proteins / metabolism
  • Animals
  • Hair Follicle / physiology*
  • Homeodomain Proteins / genetics
  • Lymphatic Vessels / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Regeneration*
  • Stem Cell Niche / physiology*
  • Stem Cells / metabolism
  • Stem Cells / physiology*
  • Tumor Suppressor Proteins / genetics

Substances

  • ANGPTL7 protein, mouse
  • Angiopoietin-Like Protein 4
  • Angiopoietin-Like Protein 7
  • Angiopoietin-like Proteins
  • Angptl4 protein, mouse
  • Homeodomain Proteins
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein