Howard Hughes Medical Institute, Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10065, USA.
Department of Surgery, Plastic and Reconstructive Surgery Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Science. 2019 Dec 6;366(6470):1218-1225. doi: 10.1126/science.aay4509. Epub 2019 Oct 31.
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 (), promoting lymphatic drainage. Activated SCs switch to , 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.
组织依赖于干细胞 (SCs) 来维持体内平衡和进行伤口修复。SCs 存在于专门的微环境（龛）中，这些龛的复杂性及其在组织生长中的作用仍在不断揭示。在这里，我们将淋巴管鉴定为关键的 SC 龛位组成部分。在皮肤中，淋巴管围绕毛囊 (HF)SCs 形成紧密的网络。当 HFs 再生时，淋巴管-SC 连接变得动态化。利用小鼠模型，我们揭示了控制淋巴管行为的 SC 中的分泌组开关。静止的 SC 表达血管生成素样蛋白 7 ()，促进淋巴管引流。激活的 SC 切换到 ，引发短暂的淋巴管分离和减少引流。当淋巴管受到干扰或分泌组开关被破坏时，HFs 过早循环，组织再生变得不同步。在揭示淋巴管作为关键 SC 龛位元素的过程中，我们了解了 SC 如何在整个组织中协调其活动。
