A spatial human thymus cell atlas mapped to a continuous tissue axis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.