Puthier Denis, Joly Florence, Irla Magali, Saade Murielle, Victorero Geneviève, Loriod Béatrice, Nguyen Catherine
Technologies Avancées pour le Génome et la Clinique/ERM 206, Parc Scientifique de Luminy, 13288 Marseille cedex 09, France.
J Immunol. 2004 Nov 15;173(10):6109-18. doi: 10.4049/jimmunol.173.10.6109.
The thymus is the primary site of T cell lymphopoiesis. To undergo proper differentiation, developing T cells follow a well-ordered genetic program that strictly depends on the heterogeneous and highly specialized thymic microenvironment. In this study, we used microarray technology to extensively describe transcriptional events regulating alphabeta T cell fate. To get an integrated view of these processes, both whole thymi from genetically engineered mice together with purified thymocytes were analyzed. Using mice exhibiting various transcriptional perturbations and developmental blockades, we performed a transcriptional microdissection of the organ. Multiple signatures covering both cortical and medullary stroma as well as various thymocyte maturation intermediates were clearly defined. Beyond the definition of histological and functional signatures (proliferation, rearrangement), we provide the first evidence that such an approach may also highlight the complex cross-talk events that occur between maturing T cells and stroma. Our data constitute a useful integrated resource describing the main gene networks set up during thymocyte development and a first step toward a more systematic transcriptional analysis of genetically modified mice.
胸腺是T细胞淋巴细胞生成的主要场所。为了进行适当的分化，发育中的T细胞遵循一个严格依赖于异质性和高度专业化胸腺微环境的有序遗传程序。在本研究中，我们使用微阵列技术广泛描述调节αβ T细胞命运的转录事件。为了全面了解这些过程，我们分析了来自基因工程小鼠的整个胸腺以及纯化的胸腺细胞。利用表现出各种转录扰动和发育阻滞的小鼠，我们对该器官进行了转录微观剖析。明确界定了涵盖皮质和髓质基质以及各种胸腺细胞成熟中间体的多种特征。除了组织学和功能特征（增殖、重排）的定义之外，我们还提供了首个证据，表明这种方法还可能突出成熟T细胞与基质之间发生的复杂相互作用事件。我们的数据构成了一个有用的综合资源，描述了胸腺细胞发育过程中建立的主要基因网络，也是朝着对基因修饰小鼠进行更系统的转录分析迈出的第一步。
