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

摘要 血液和皮肤等高度再生的组织可能在体内利用血管作为双重角色 组织生长功能：一种是供氧/营养，另一种是调节组织干细胞 通过信号进行活动。相关证据表明，皮肤内皮细胞可能起到 向成年毛囊干细胞(HfSCs)发送信号，调节其静止状态。至 证明这一点，我们需要对内皮细胞中的信号分子进行基因打靶，进而 会影响干细胞的活性。此外，最近关于皮肤血管系统的工作探索了 淋巴管而不是血管在成人HFSC激活中的作用。最后，皮肤的范围 毛发周期中的血管重塑及其遗传控制还知之甚少。我们 建议在小鼠身上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。我们的鼠标模型提供了一个令人兴奋的切入点，以解决交叉- HfSCs与邻近内皮细胞的通讯，探讨其生理功能 相关性，并首次将内皮细胞作为成人真正的信号利基 Hfscs。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.