Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin

摘要 高度再生的组织，如血液和皮肤，可以利用血管作为双重参与者， 组织生长功能：一个是提供O2/营养物质，另一个是调节组织干细胞 通过信号活动。相关证据表明，皮肤内皮细胞可能作为 成年毛囊干细胞（HFSC）的信号小生境，调节它们的静止。到 为了证明这一点，我们需要内皮细胞中信号分子的基因靶向， 会影响干细胞的活性此外，最近对皮肤脉管系统的研究探讨了 淋巴管，但不是血管在成人HFSC激活。最后，皮肤的程度 对毛发周期中的脉管系统重塑及其遗传控制知之甚少。我们 我建议在小鼠中使用遗传和基因组相结合的方法来解决所有这些问题 问题.我们的小鼠模型提供了一个令人兴奋的切入点，以解决交叉- HFSC与邻近内皮细胞的通讯，以探测其生理学特性。 相关性，并首次将内皮细胞作为成人的真正信号微环境， HFSC。这项工作将在未来对人类皮肤再生研究和 对皮肤血管疾病有更深入的了解。

Abstract Highly regenerative tissues such as blood and skin may utilize blood vessels as dual players in tissue growth functions: one in supplying O2/nutrients and another in regulating tissue stem cell activity via signaling. Correlative evidence suggest that skin endothelial cells may act as signaling niches to adult hair follicle stem cells (HFSCs), regulating their quiescence. To demonstrate this, we need gene targeting of signaling molecules in endothelial cells that in turn would affect stem cell activity. Furthermore, recent work on skin vasculature probed a role of lymphatic vessels but not of blood vessels in adult HFSC activation. Finally, the extent of skin vasculature remodeling and its genetic control during the hair cycle are poorly understood. We propose to use a combined genetic and genomic approach in mice to address all these questions. Our mouse models provide an exciting entry point to address the cross- communication of HFSCs with the neighboring endothelial cells, to probe its physiological relevance, and to place endothelial cells for the first time as bona-fide signaling niches for adult HFSCs. This work will have future broad relevance for human skin regeneration studies and for more in depth understanding of skin vasculature disease.