Metabolic Control of Hair Follicle Stem Cell Homeostasis and Tumorigenesis

项目摘要/摘要 目前的项目建立在我们以前的努力的基础上，定义和表征了 表皮。我们证明毛囊干细胞是鳞状细胞癌的起源细胞，并且 这些细胞与生俱来的静止状态是一种肿瘤抑制机制。目前的提案 旨在了解新陈代谢在维持hfSCs和启动hfscs的能力中所起的作用。 肿瘤发生学。我们的初步数据表明，hfSCs具有独特的新陈代谢模式，我们 试图了解这种新陈代谢状态是否是维持这些细胞静止、多能干细胞所必需的 细胞。我们将扩展我们对hfSCs的描述，以包括代谢组学方法并确定 代谢途径的改变是否会扰乱它们的自我更新或分化。此外，在我们的 可诱导的肿瘤启动模型，我们将能够表征任何代谢转变的全部范围， 这是第一次在体内发生。我们预计，这些实验将发现新的机制， HFSC生物学，甚至可能指向针对HFSC发起的肿瘤的新的靶向治疗。

PROJECT SUMMARY/ABSTRACT The current project builds on our previous efforts to define and characterize cancer cells of origin within the epidermis. We demonstrated that hair follicle stem cells are cells of origin for squamous cell carcinoma, and that the inherent quiescence of these cells acts as a tumor suppressor mechanism. The current proposal seeks to understand the role metabolism plays in both maintaining HFSCs, and also in their ability to initiate tumorigenesis. Our preliminary data suggests that HFSCs possess a unique mode of metabolism, and we seek to understand if this metabolic state is necessary to maintain these cells as quiescent, multipotent stem cells. We will extend our characterization of HFSCs to include metabolomics approaches and determine whether alteration of metabolic pathways disrupts their self-renewal or differentiation. Furthermore, with our inducible tumor initiation model, we will be able to characterize the full extent of any metabolic transitions that occur in vivo for the first time. We expect that these experiments will uncover novel mechanisms that regulate HFSC biology, and perhaps even point towards new targeted therapeutics for HFSC initiated tumors.