Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.
Forging T-Lymphocyte Identity: Intersecting Networks of Transcriptional Control.
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锻造T淋巴细胞身份：转录控制的网络相交。
DOI：
10.1016/bs.ai.2015.09.002
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发表时间：
2016
影响因子：
--
通讯作者：
Champhekar A
中科院分区：
文献类型：
--
作者：
Rothenberg EV;Ungerbäck J;Champhekar A
T淋巴细胞发育通过Notch途径需要持续的环境信号而从其他淋巴发育程序中分支出来。在胸腺中，Notch信号传导诱导一系列T谱系调节因子，这些调节因子通过不同的步骤共同产生T细胞身份。这个过程涉及T细胞身份基因的阶段性激活和祖细胞遗传的调节基因的阶段性抑制，一旦它们在自我更新和人口扩张中的作用不再需要。随着最近对与T细胞亚群广泛共享转录调控程序的先天类淋巴细胞（ILC）的表征，T细胞身份可以越来越多地被视为以模块术语定义，因为选择和致动效应子功能的过程可能与产生和选择克隆独特的T细胞受体结构的过程分离。不同类型的T细胞和ILC的发育途径的区别在于，在细胞获得用于选择效应子功能的几乎共同的调节机制之前，基因重排、选择和抗原接触的先决条件的数量。在这里，与Notch信号在T-谱系规范的主要类别的转录因子进行了讨论，在这些程序中的作用，在不同阶段的靶基因谱的证据，和他们的交叉调节和相互合作的行动。具体主题包括PU.1和加塔-3的Notch调节、PU.1-Notch竞争、PU.1和加塔-3之间的关系，以及E蛋白、Bcl 11b和加塔-3在引导T细胞身份获得同时避免重定向到ILC命运中的作用。
T lymphocyte development branches off from other lymphoid developmental programs through its requirement for sustained environmental signals through the Notch pathway. In the thymus, Notch signaling induces a succession of T-lineage regulatory factors that collectively create the T-cell identity through distinct steps. This process involves both the staged activation of T-cell identity genes and the staged repression of progenitor-cell-inherited regulatory genes once their roles in self-renewal and population expansion are no longer needed. With the recent characterization of Innate Lymphoid Cells (ILCs) that share transcriptional regulation programs extensively with T cell subsets, T-cell identity can increasingly be seen as defined in modular terms, as the processes selecting and actuating effector function are potentially detachable from the processes generating and selecting clonally unique T-cell receptor structures. The developmental pathways of different classes of T cells and ILCs are distinguished by the numbers of prerequisites of gene rearrangement, selection, and antigen contact before the cells gain access to nearly-common regulatory mechanisms for choosing effector function. Here, the major classes of transcription factors that interact with Notch signals during T-lineage specification are discussed in terms of their roles in these programs, the evidence for their spectra of target genes at different stages, and their cross-regulatory and cooperative actions with each other. Specific topics include Notch modulation of PU.1 and GATA-3, PU.1-Notch competition, the relationship between PU.1 and GATA-3, and the roles of E proteins, Bcl11b, and GATA-3 in guiding acquisition of T-cell identity while avoiding redirection to an ILC fate.