Browse by author
Lookup NU author(s): Justin Engelbert, Emily Stephenson, Dr David Crossland, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.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.
Author(s): Yayon N, Kedlian VR, Boehme L, Suo C, Wachter BT, Beuschel RT, Amsalem O, Polanski K, Koplev S, Tuck E, Dann E, Van Hulle J, Perera S, Putteman T, Predeus AV, Dabrowska M, Richardson L, Tudor C, Kreins AY, Engelbert J, Stephenson E, Kleshchevnikov V, De Rita F, Crossland D, Bosticardo M, Pala F, Prigmore E, Chipampe N-J, Prete M, Fei L, To K, Barker RA, He X, Van Nieuwerburgh F, Bayraktar OA, Patel M, Davies EG, Haniffa MA, Uhlmann V, Notarangelo LD, Germain RN, Radtke AJ, Marioni JC, Taghon T, Teichmann SA
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2024
Volume: 635
Issue: 8039
Pages: 708-718
Print publication date: 21/11/2024
Online publication date: 20/11/2024
Acceptance date: 13/08/2024
Date deposited: 05/12/2024
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-024-07944-6
DOI: 10.1038/s41586-024-07944-6
Data Access Statement: The annotated fetal and paediatric integrated scRNA-seq atlas and Visium objects for this study can be explored online https://cellxgene.cziscience.com/collections/fc19ae6c-d7c1-4dce-b703-62c5d52061b4. Paediatric CITE-seq data can be visualised and explored using a custom ShinyApp (https://ccgg.ugent.be/shiny/htsa_thymocyte_citeseq/). Sequencing data for the newly generated libraries for scRNA-seq and Visium data were uploaded to ENA under accession code PRJEB77091. Several samples were obtained under consent agreements that require data release with managed access, which is why these were deposited at EGA under accession code EGAD00001015384. Imaging data for Visium samples were deposited at BioImage Archive under accession number S-BIAD1257. CITE-seq data were uploaded to the GEO under accession number GSE271304. More at https://www.nature.com/articles/s41586-024-07944-6#data-availability and https://www.nature.com/articles/s41586-024-07944-6#code-availability
Altmetrics provided by Altmetric
