Guest editorial: Molecular mechanisms of lymphocyte development: recent findings
Guest editorial: Molecular mechanisms of lymphocyte development: recent findings
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客座社论：淋巴细胞发育的分子机制：最新发现
DOI：
10.1007/s12185-014-1645-4
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发表时间：
2014
影响因子：
2.1
通讯作者：
Takafumi Yokota
中科院分区：
文献类型：
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作者：
Okada Y;Funahashi N;Tanaka T;Nishiyama Y;Yuan L;Shirakura K;Turjman AS;Kano Y;Naruse H;Suzuki A;Sakai M;Zhixia J;Kitajima K;Ishimoto K;Hino N;Kondoh M;Mukai Y;Nakagawa S;Garcia-Cardena G;Aird WC;Doi T.;Takafumi Yokota
淋巴细胞在哺乳动物免疫系统中发挥着重要作用。在成体生物体中，这些细胞通过逐步分化过程从主要存在于骨髓中的造血干细胞（HSC）产生。这一过程已得到充分研究，并且是细胞分化的范例，原始细胞和多能细胞通过该过程获得特定的功能和位置。现已证明，各种细胞因子、细胞表面分子和转录因子协同作用、分层次地构成了淋巴细胞生成的精细机制。然而，一个重要的问题仍然存在：如何协调和协调这些不同的元素？虽然细胞因子信号传导和转录因子长期以来一直是研究的主题，但淋巴细胞生成的分子机制现在正在表观遗传调控和 microRNA 方面得到广泛研究。在本期中，该领域的专家研究人员撰写的四篇评论文章向《血液学进展》读者介绍了连续研究的最新发现（图 1）。转录因子 Ikaros 作为淋巴细胞分化早期的重要调节因子已被广泛研究。最近的研究表明，Ikaros 积极参与广泛的淋巴细胞分化过程。作为连接转录复合物和染色质重塑网络的组成部分，该蛋白质进一步引起了人们的广泛关注。 Ikaros 研究的领先科学家和先驱 Yoshida 和 Georgopoulos 对这种蛋白质如何促进正常淋巴细胞生成和预防白血病生成进行了全面综述 [1]。淋巴细胞分化需要淋巴相关基因的激活和其他谱系相关基因的失活。现在人们认识到，淋巴细胞生成的早期阶段是由异质 HSC 群体通过基因表达的异步途径进行的。然而，似乎有一种基本机制可以通过协调各种基因的表达来引导造血干细胞走向淋巴谱系。 Yokota 和 Kanakura 引入了全局染色质重塑蛋白，特别是富含 AT 的特殊序列结合蛋白 1 (Satb1)，作为早期淋巴细胞分化的重要调节因子 [2]。淋巴细胞被赋予了克服多种病原体的特殊基因重组能力。虽然免疫球蛋白基因或 T 细胞受体基因的重组对于适应性免疫系统至关重要，但该过程会因引入双链 DNA 断裂而增加突变的风险。 Shimazaki 和 Lieber 对理解淋巴细胞生成中的基因重组机制做出了卓越的贡献，他们提出了通过染色质结构和组蛋白修饰精细控制重组的最新发现 [3]。
Lymphocytes play vital roles in the mammalian immune system. In adult organisms, these cells arise, via a step-bystep differentiation process, from hematopoietic stem cells (HSCs) residing mainly in the bone marrow. This process has been well studied and is a paradigm of cell differentiation by which primitive and multipotent cells acquire specific functions and locations. It has been demonstrated that various cytokines, cell-surface molecules, and transcription factors serve synergistically and hierarchically to constitute the exquisite mechanism of lymphopoiesis. However, an important question remains: how are these diverse elements harmonized and orchestrated? While cytokine signaling and transcription factors have long been a topic of investigation, molecular mechanisms of lymphopoiesis are now being studied extensively in terms of epigenetic regulation and microRNAs. In this issue, four review articles by expert investigators in this field present up-to-date findings from continuous studies (Fig. 1) to Progress In Hematology readers. The transcription factor Ikaros has been extensively studied as an essential regulator of the early stages of lymphocyte differentiation. Recent studies have revealed that Ikaros is actively involved in a broad range of lymphocyte differentiation processes. The protein has further attracted much attention as an integral component connecting the transcription complex and chromatin-remodeling network. Yoshida and Georgopoulos, leading scientists and pioneers of research on Ikaros, present a comprehensive review on how this protein promotes normal lymphopoiesis and prevents leukemogenesis [1]. Lymphocyte differentiation requires both activation of lymphoid-related genes and inactivation of other lineagerelated genes. It is now appreciated that the early stages of lymphopoiesis proceed from a heterogeneous population of HSCs through asynchronous pathways of gene expression. However, there seems to be a fundamental mechanism that directs HSCs toward the lymphoid lineage by orchestrating the expression of various genes. Yokota and Kanakura introduce global chromatin-remodeling proteins, particularly Special AT-rich sequence-binding protein 1 (Satb1), as important regulators of early lymphocyte differentiation [2].Lymphocytes are endowed with a special gene recombination ability to overcome diverse pathogens. While recombination of the immunoglobulin gene or the T cell receptor genes is vital to the adaptive immune system, the process increases the risk of mutation by introduction of double-strand DNA breaks. Shimazaki and Lieber, who have made a remarkable contribution to the understanding of gene recombination mechanisms in lymphopoiesis, present recent findings on the elaborate control of recombination by chromatin structure and histone modification [3].