Epithelial Cell Biology Group, Cancer Cell Biology Programme, Spanish Cancer Research Centre (CNIO), Madrid, Spain.
Section of Cell Biology and Physiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
EMBO J. 2019 Oct 1;38(19):e101688. doi: 10.15252/embj.2019101688. Epub 2019 Sep 2.
Lymphatic vessels are essential for skin fluid homeostasis and immune cell trafficking. Whether the lymphatic vasculature is associated with hair follicle regeneration is, however, unknown. Here, using steady and live imaging approaches in mouse skin, we show that lymphatic vessels distribute to the anterior permanent region of individual hair follicles, starting from development through all cycle stages and interconnecting neighboring follicles at the bulge level, in a stem cell-dependent manner. Lymphatic vessels further connect hair follicles in triads and dynamically flow across the skin. At the onset of the physiological stem cell activation, or upon pharmacological or genetic induction of hair follicle growth, lymphatic vessels transiently expand their caliber suggesting an increased tissue drainage capacity. Interestingly, the physiological caliber increase is associated with a distinct gene expression correlated with lymphatic vessel reorganization. Using mouse genetics, we show that lymphatic vessel depletion blocks hair follicle growth. Our findings point toward the lymphatic vasculature being important for hair follicle development, cycling, and organization, and define lymphatic vessels as stem cell niche components, coordinating connections at tissue-level, thus provide insight into their functional contribution to skin regeneration.
淋巴管对于皮肤液稳态和免疫细胞迁移至关重要。然而，淋巴管是否与毛囊再生有关尚不清楚。在这里，我们使用小鼠皮肤的稳定和实时成像方法，显示淋巴管从发育到所有周期阶段分布到单个毛囊的前永久性区域，并以干细胞依赖性的方式在隆突水平上连接相邻的毛囊。淋巴管进一步连接三联体中的毛囊，并在皮肤中动态流动。在生理干细胞激活开始时，或者在药理学或基因诱导毛发生长时，淋巴管暂时扩大其口径，表明组织引流能力增加。有趣的是，生理口径增加与与淋巴管重排相关的特定基因表达相关联。使用小鼠遗传学，我们表明淋巴管耗竭会阻止毛囊生长。我们的研究结果表明，淋巴管对于毛囊的发育、循环和组织排列很重要，并将淋巴管定义为干细胞龛的组成部分，协调组织水平的连接，从而深入了解它们对皮肤再生的功能贡献。
