Spatial Mapping of Thymic Stromal Microenvironments Reveals Unique Features Influencing T Lymphoid Differentiation
Spatial Mapping of Thymic Stromal Microenvironments Reveals Unique Features Influencing T Lymphoid Differentiation
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DOI：
10.1016/j.immuni.2009.09.024
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发表时间：
2009-12-18
期刊：
影响因子：
32.4
通讯作者：
Petrie, Howard T.
中科院分区：
文献类型：
--
作者：
Griffith, Ann V.;Fallahi, Mohammad;Petrie, Howard T.
造血祖细胞与胸腺微环境的相互作用诱导它们增殖，采用T谱系命运，并不对称地分化成多个功能谱系。不同发育阶段的祖细胞在胸腺内分层，这意味着相应的微环境为在它们之间迁移的祖细胞提供了不同的信号。这些差异在很大程度上仍然没有明确的定义。在这里，我们使用物理和计算的方法来生成一个全面的空间地图的基质基因表达的胸腺。虽然大多数基质区域的特点是一个独特的基因表达签名，中央皮层缺乏独特的功能。相反，该区域的一个关键功能似乎是隔离在皮质末端发现的独特微环境，从而调节在它们之间移动的祖细胞的相对接近度。我们的研究结果迫使重新审视细胞迁移，谱系规范，增殖是如何控制胸腺结构，并提供了一个深入的资源，这种控制的全球特征。
Interaction of hematopoietic progenitors with the thymic microenvironment induces them to proliferate, adopt the T lineage fate, and asymmetrically diverge into multiple functional lineages. Progenitors at various developmental stages are stratified within the thymus, implying that the corresponding microenvironments provide distinct sets of signals to progenitors migrating between them. These differences remain largely undefined. Here we used physical and computational approaches to generate a comprehensive spatial map of stromal gene expression in the thymus. Although most stromal regions were characterized by a unique gene expression signature, the central cortex lacked distinctive features. Instead, a key function of this region appears to be the sequestration of unique microenvironments found at the cortical extremities, thus modulating the relative proximity of progenitors moving between them. Our findings compel reexamination of how cell migration, lineage specification, and proliferation are controlled by thymic architecture and provide an in-depth resource for global characterization of this control.