The Regulation of Delta-like 4 in Thymic Epithelial Cells as a Model for Organ Structure Affecting Gene Regulation

胸腺上皮细胞中 Delta-like 4 的调控作为影响基因调控的器官结构模型

• 批准号: RGPIN-2016-06592
• 负责人: ZunigaPflucker, JuanCarlos
• 金额: $ 3.21万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=670006
• 关键词: Regulation; Delta; like; Thymic; Epithelial

The thymus is the primary site responsible for the production of T cells from bone marrow-derived lymphocyte progenitors. Key to this function is the expression of the Delta-like 4 (Dll4) gene product on the surface of thymic epithelial cells (TECs). Despite playing an indispensable role in T-cell development, the molecular factors controlling the expression of Dll4 remain largely unexplored. While we know that the TECs must be maintained in a 3-dimensional (3D) structure to successfully express Dll4, we do not know why that is nor what molecules connect 3D structure to Dll4 expression. Our work aims to understand the link between the 3D thymic microenvironment and correct gene expression in TECs. In doing so, we will gain a better understanding of how the thymus functions. We also feel that our work will result in the discovery of shared pathways between TECs and other cell types requiring 3D structure to properly function (i.e. hepatocytes, and mammary epithelial cells). This understanding will provide valuable information and lay the foundation for research into improving methods for tissue regeneration and bioengineering.

胸腺是负责从骨髓来源的淋巴细胞祖细胞产生T细胞的主要部位。这种功能的关键是在胸腺上皮细胞（TEC）的表面上表达δ样4（Dll 4）基因产物。尽管在T细胞发育中起着不可或缺的作用，但控制Dll4表达的分子因子在很大程度上仍未被探索。虽然我们知道TEC必须保持在三维（3D）结构中才能成功表达Dll4，但我们不知道为什么会这样，也不知道是什么分子将3D结构与Dll4表达联系起来。我们的工作旨在了解3D胸腺微环境与TEC中正确基因表达之间的联系。通过这样做，我们将更好地了解胸腺的功能。我们还认为，我们的工作将导致发现TEC和其他需要3D结构才能正常工作的细胞类型（即肝细胞和乳腺上皮细胞）之间的共享途径。这一认识将提供有价值的信息，并为研究改进组织再生和生物工程方法奠定基础。