英国威康桑格研究所Sarah A. Teichmann，比利时根特大学诊断科学系Tom Taghon，英国欧洲分子生物学实验室John C. Marioni，美国国家过敏和传染病研究所Andrea J. Radtke和Ronald N. Germain共同合作，近期取得重要工作进展。他们研究绘制了映射到连续组织轴的空间人类胸腺细胞图谱。相关研究成果2024年11月20日在线发表于《自然》杂志上。

据介绍，T细胞由循环的前体细胞发育而来，前体细胞进入胸腺，并通过支持其成熟和选择的区域特化迁移。在人类中，这一过程始于胎儿早期发育，在青春期胸腺退化之前一直非常活跃。

为了绘制出生前和出生后早期这一过程的显微解剖学基础，研究人员建立了胸腺的定量形态学框架（皮质髓质轴），并用它进行了空间分辨分析。

通过将该框架应用于多模式单细胞图谱、空间转录组学和高分辨率多重成像数据，研究人员证明了在胎儿发育中期开始时，小叶细胞因子网络、典型胸腺细胞轨迹和胸腺上皮细胞分布的建立。

研究人员精确定位胸腺上皮细胞祖细胞的组织生态位，和与胸腺小体相关的不同亚型，并确定CD4和CD8 T细胞谱系进入髓质的时间差异。

总之，这一研究为详细了解T淋巴细胞发育提供了基础，并辅以可应用于任何组织的跨平台成像数据分析、注释和OrganisAxis构建（TissueTag）的整体工具包。

附：英文原文

Title: A spatial human thymus cell atlas mapped to a continuous tissue axis

Author: Yayon, Nadav, Kedlian, Veronika R., Boehme, Lena, Suo, Chenqu, Wachter, Brianna T., Beuschel, Rebecca T., Amsalem, Oren, Polanski, Krzysztof, Koplev, Simon, Tuck, Elizabeth, Dann, Emma, Van Hulle, Jolien, Perera, Shani, Putteman, Tom, Predeus, Alexander V., Dabrowska, Monika, Richardson, Laura, Tudor, Catherine, Kreins, Alexandra Y., Engelbert, Justin, Stephenson, Emily, Kleshchevnikov, Vitalii, De Rita, Fabrizio, Crossland, David, Bosticardo, Marita, Pala, Francesca, Prigmore, Elena, Chipampe, Nana-Jane, Prete, Martin, Fei, Lijiang, To, Ken, Barker, Roger A., He, Xiaoling, Van Nieuwerburgh, Filip, Bayraktar, Omer Ali, Patel, Minal, Davies, E Graham, Haniffa, Muzlifah A., Uhlmann, Virginie, Notarangelo, Luigi D., Germain, Ronald N., Radtke, Andrea J., Marioni, John C., Taghon, Tom, Teichmann, Sarah A.

Issue&Volume: 2024-11-20

Abstract: T cells develop from circulating precursor cells, which enter the thymus and migrate through specialized subcompartments that support their maturation and selection1. In humans, this process starts in early fetal development and is highly active until thymic involution in adolescence. To map the microanatomical underpinnings of this process in pre- and early postnatal stages, we established a quantitative morphological framework for the thymus—the Cortico-Medullary Axis—and used it to perform a spatially resolved analysis. Here, by applying this framework to a curated multimodal single-cell atlas, spatial transcriptomics and high-resolution multiplex imaging data, we demonstrate establishment of the lobular cytokine network, canonical thymocyte trajectories and thymic epithelial cell distributions by the beginning of the the second trimester of fetal development. We pinpoint tissue niches of thymic epithelial cell progenitors and distinct subtypes associated with Hassall’s corpuscles and identify divergence in the timing of medullary entry between CD4 and CD8 T cell lineages. These findings provide a basis for a detailed understanding of T lymphocyte development and are complemented with a holistic toolkit for cross-platform imaging data analysis, annotation and OrganAxis construction (TissueTag), which can be applied to any tissue.

DOI: 10.1038/s41586-024-07944-6

Source: https://www.nature.com/articles/s41586-024-07944-6