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

胸腺是从骨髓来源的淋巴祖细胞产生T细胞的主要部位。这一功能的关键是胸腺上皮细胞(TECs)表面Delta样4(DLL4)基因产物的表达。尽管在T细胞发育中发挥了不可或缺的作用，但控制DLL4表达的分子因素仍然很大程度上尚不清楚。虽然我们知道TECs必须保持在三维(3D)结构中才能成功表达DLL4，但我们不知道这是为什么，也不知道什么分子将3D结构与DLL4表达联系起来。我们的工作旨在了解3D胸腺微环境和TEC中正确的基因表达之间的联系。在这样做的过程中，我们将对胸腺的功能有更好的了解。我们还认为，我们的工作将导致发现TECs和其他需要3D结构才能正常发挥功能的细胞类型(即肝细胞和乳腺上皮细胞)之间的共同途径。这一认识将提供有价值的信息，并为研究组织再生和生物工程的改进方法奠定基础。

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.