@article{4661,
  keywords = {Computational models, Data integration, Lymphocyte differentiation, Lymphopoiesis, Software},
  author = {Nadav Yayon and Veronika R. Kedlian and Lena Boehme and Chenqu Suo and Brianna T. Wachter and Rebecca T. Beuschel and Oren Amsalem and Krzysztof Polanski and Simon Koplev and Elizabeth Tuck and Emma Dann and Jolien Van Hulle and Shani Perera and Tom Putteman and Alexander V. Predeus and Monika Dabrowska and Laura Richardson and Catherine Tudor and Alexandra Y. Kreins and Justin Engelbert and Emily Stephenson and Vitalii Kleshchevnikov and Fabrizio De Rita and David Crossland and Marita Bosticardo and Francesca Pala and Elena Prigmore and Nana-Jane Chipampe and Martin Prete and Lijiang Fei and Ken To and Roger A. Barker and Xiaoling He and Filip Van Nieuwerburgh and Omer Ali Bayraktar and Minal Patel and E. Graham Davies and Muzlifah A. Haniffa and Virginie Uhlmann and Luigi D. Notarangelo and Ronald N. Germain and Andrea J. Radtke and John C. Marioni and Tom Taghon and Sarah A. Teichmann},
  title = {A spatial human thymus cell atlas mapped to a continuous tissue axis},
  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.},
  year = {2024},
  journal = {Nature},
  volume = {635},
  pages = {708-718},
  month = {2024-11},
  issn = {1476-4687},
  url = {https://www.nature.com/articles/s41586-024-07944-6},
  doi = {10.1038/s41586-024-07944-6},
  language = {en},
}