胸腺上皮前体（干）细胞特异标志的筛选及功能鉴定

项目名称： 胸腺上皮前体（干）细胞特异标志的筛选及功能鉴定

项目编号： No.31200681

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 罗海英

作者单位： 中国科学院动物研究所

项目金额： 20万元

中文摘要： 各种因素引起的胸腺功能受损及缺失均会引起T淋巴细胞发育异常，严重影响机体细胞免疫力。胸腺再生和功能重建是解决这一问题的理想方法。胸腺上皮细胞(TECs)为T细胞的发育成熟提供必要的微环境。研究证明，皮质及髓质TECs均来源于同一胸腺上皮前体（干）细胞(TEPCs)，且体内移植TEPCs能够重建有功能的胸腺组织。但目前仍缺乏筛选TEPCs的特异性标志，极大地限制了对TEPCs的基础研究及应用。基于我们前期工作，本课题从自主创建实验方法入手，应用干细胞生物学、分子细胞生物学以及基因组学等最新的理论与技术，筛选TEPCs特异性标志；并在体内移植模型及自行建立的TEPCs体外扩增及诱导体系中，对分选的不同细胞群体进行特性鉴定及功能分析，从而获得TEPCs特异的新标志，并对TEPCs的定向分化机制进行初步探讨，为TEPCs的生物学研究及其应用提供必要的研究手段与基础。

中文关键词： 胸腺上皮细胞；胸腺上皮前体（干）细胞；分化；发育；T细胞

英文摘要： A functional thymus provides a specialized microenvironment for the development of T cells in which the epithelial component is indispensable for the positive and negative selection. The abnormal thymic epithelial cells (TECs) can disrupt the development of T cells and result in immunodeficiency and autoimmune disorders. An ideal strategy for TEC regeneration can enhance endogenous thymic function. It has been conformed that the cortical and the medullary epithelial cells (cTECs and mTECs) can be derived from a common epithelial progenitor cell (TEPC), and a single TEPC can give rise to a complete and functional thymic microenvironment, suggesting that TEPC-based regeneration therapies could be developed for thymus disorders. However, the lack of specific cell-surface markers has hampered the characterization of TEPC and its application. Identification and characterization of TEPCs are essential for establishing stem cell-based therapies for immunodeficiency and autoimmune. In this project, our program is to identify the specific cell-surface markers of TEPCs and investigate the mechanism of TEPC differentiation and self-renewing deeply by using the approaches of stem cell biology, molecular and cellular biology and genomics on the basis of our preliminary work. The characteristics and functions of TEPCs being i

英文关键词： Thymic epithelial cell；thymic epithelial progenitor cell；differentiation；development；T cell