Molecular characterization of thymic epithelium

胸腺上皮的分子特征

• 批准号: 6718185
• 负责人: ANDREW G FARR
• 金额: $ 18.15万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6718185
• 关键词: age difference; cell differentiation; cell population study; epithelium; gene expression; gene expression profiling; immunogenetics; laboratory mouse; laser capture microdissection; microarray technology; polymerase chain reaction; thymus

DESCRIPTION (provided by applicant): Based on work supported by the parent application concerning the role of FGF family members in thymic epithelium (TE) development and function, we have proposed the hypothesis that multi-potential pharyngeal endodermal progenitor cells persist within the adult thymus and in other endodermally-derived organs and tissues. Within the thymus, these cells would play a central role in maintaining medullary epithelial heterogeneity, while in extrathymic, endodermally-derived tissues, these progenitor cells could retain the capacity to support thymopoietic environments. Because of the commingled nature of the epithelia within the thymus and in other epithelial tissues, traditional approaches to analyze gene expression are not feasible and in situ approaches are too labor and time intensive to rapidly survey the expression of a large number of genes, Furthermore, this latter approach would not identify novel or unanticipated gene products. The activities proposed here will develop the infrastructure and experimental approaches necessary to test several postulates of this hypothesis. Specifically, we wish to employ laser capture micro-dissection to recover thymic tissue components and to utilize the recovered RNA to probe the profiles gene expression by defined compartments of thymic epithelium. This approach has been used successfully in several studies of the thymic environment, thus speaking to the utility of the approach, but has not been widely employed due to the novelty of the required instrumentation. This application requests support to bring state-of the art technologies to explore the character and regulation of the thymic microenvironment. The information gained is likely to provide new insight into several important areas of thymus biology, including the regulation of thymic epithelial development, which in turn is likely to be centrally involved in the maintenance of self tolerance and the control of age-related thymic involution.

描述（由申请人提供）：基于父母申请支持的关于FGF家族成员在胸腺上皮（TE）发育和功能中的作用的工作，我们提出了多潜能咽部内胚层祖细胞存在于成人胸腺和其他内胚层来源的器官和组织中的假设。在胸腺内，这些细胞将在维持髓质上皮异质性中发挥核心作用，而在胸腺外、内胚层来源的组织中，这些祖细胞可以保留支持胸腺生成环境的能力。由于胸腺上皮和其他上皮组织的混合性质，传统的分析基因表达的方法是不可行的，而原位方法过于费力和费时，无法快速调查大量基因的表达，此外，后一种方法不能识别新的或意想不到的基因产物。这里提出的活动将发展必要的基础设施和实验方法，以检验这一假设的若干假设。具体来说，我们希望采用激光捕获显微解剖来恢复胸腺组织成分，并利用回收的RNA来探测胸腺上皮特定区室的基因表达谱。该方法已在胸腺环境的几项研究中成功使用，因此说明了该方法的实用性，但由于所需仪器的新颖性，尚未广泛应用。该应用程序请求支持，以带来最先进的技术来探索胸腺微环境的特征和调节。所获得的信息可能为胸腺生物学的几个重要领域提供新的见解，包括胸腺上皮发育的调节，而胸腺上皮发育又可能集中参与维持自我耐受性和控制与年龄相关的胸腺退化。