Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Immunol Rev. 2010 Nov;238(1):93-109. doi: 10.1111/j.1600-065X.2010.00957.x.
Lymphopoiesis generates mature B, T, and NK lymphocytes from hematopoietic stem cells via a series of increasingly restricted developmental intermediates. The transcriptional networks that regulate these fate choices are composed of both common and lineage-specific components, which combine to create a cellular context that informs the developmental response to external signals. E proteins are an important factor during lymphopoiesis, and E2A in particular is required for normal T- and B-cell development. Although the other E proteins, HEB and E2-2, are expressed during lymphopoiesis and can compensate for some of E2A's activity, E2A proteins have non-redundant functions during early T-cell development and at multiple checkpoints throughout B lymphopoiesis. More recently, a role for E2A has been demonstrated in the generation of lymphoid-primed multipotent progenitors and shown to favor their specification toward lymphoid over myeloid lineages. This review summarizes both our current understanding of the wide-ranging functions of E proteins during the development of adaptive lymphocytes and the novel functions of E2A in orchestrating a lymphoid-biased cellular context in early multipotent progenitors.
淋巴样细胞生成通过一系列逐渐受限的发育中间产物，从造血干细胞产生成熟的 B、T 和 NK 淋巴细胞。调节这些命运选择的转录网络由共同和谱系特异性成分组成，它们结合在一起，为对外部信号的发育反应创造了一个细胞环境。E 蛋白是淋巴样细胞生成过程中的一个重要因素，特别是 E2A 对于正常的 T 细胞和 B 细胞发育是必需的。尽管其他 E 蛋白，如 HEB 和 E2-2，在淋巴样细胞生成过程中表达，并可以补偿 E2A 的一些活性，但 E2A 蛋白在早期 T 细胞发育和 B 淋巴样细胞生成过程中的多个检查点具有非冗余功能。最近，E2A 在淋巴样前体多能祖细胞的生成中发挥了作用，并显示出有利于它们向淋巴样而不是骨髓样谱系特化的作用。这篇综述总结了 E 蛋白在适应性淋巴细胞发育过程中的广泛功能，以及 E2A 在早期多能祖细胞中协调偏向淋巴样的细胞环境中的新功能。
