Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development
Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development
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DOI：
10.1007/s12026-010-8182-x
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Zhuang, Yuan
中科院分区：
文献类型：
--
作者：
Jones, Mary Elizabeth;Zhuang, Yuan
e蛋白转录因子E2A和HEB以谱系和阶段特异性的方式发挥作用，在淋巴细胞发育过程中协调许多关键事件。通过使用单基因敲除动物，e蛋白在B淋巴细胞和t淋巴细胞发育中的功能已经被广泛研究。与主要依赖E2A的B细胞不同，T细胞受E2A和HEB的组合表达调节。因此，由于E2A和HEB的代偿功能，在单基因敲除研究中，e蛋白在t细胞发育过程中的许多作用可能被掩盖。最近，我们的实验室建立了双条件敲除模型，在t细胞发育过程中以特定阶段的方式消除E2A和HEB。这些模型与其他互补的遗传方法相结合，已经在两个主要的t细胞发育检查点中确定了新的e蛋白功能。在这里，我们将讨论e蛋白如何在β选择检查点调节t细胞受体组分的表达和细胞周期，以及它们如何在随后的t细胞受体检查点控制阳性选择、存活和谱系特异性基因表达。
The E-protein transcription factors E2A and HEB function in a lineage- and stage-specific manner to orchestrate many critical events throughout lymphocyte development. The function of E-proteins in both B- and T-lymphocyte development has been extensively studied through the use of single-gene knockout animals. Unlike B cells, which rely primarily on E2A alone, T cells are regulated by the combinatorial expression of both E2A and HEB. Therefore, many of the roles of E-proteins during T-cell development may be masked in single-gene knockout studies due to the compensatory function of E2A and HEB. More recently, our laboratory has established double-conditional knockout models to eliminate both E2A and HEB in a stage-specific manner throughout T-cell development. These models, in combination with other complimentary genetic approaches, have identified new E-protein functions at each of the two major T-cell developmental checkpoints. Here, we will discuss how E-proteins function to regulate the expression of T-cell receptor components and cell cycle at the beta-selection checkpoint, and how they control positive selection, survival, and lineage-specific gene expression at the subsequent T-cell receptor checkpoint.