TY - JOUR
KW - Computational models
KW - Data integration
KW - Lymphocyte differentiation
KW - Lymphopoiesis
KW - Software
AU - Nadav Yayon
AU - Veronika R. Kedlian
AU - Lena Boehme
AU - Chenqu Suo
AU - Brianna T. Wachter
AU - Rebecca T. Beuschel
AU - Oren Amsalem
AU - Krzysztof Polanski
AU - Simon Koplev
AU - Elizabeth Tuck
AU - Emma Dann
AU - Jolien Van Hulle
AU - Shani Perera
AU - Tom Putteman
AU - Alexander V. Predeus
AU - Monika Dabrowska
AU - Laura Richardson
AU - Catherine Tudor
AU - Alexandra Y. Kreins
AU - Justin Engelbert
AU - Emily Stephenson
AU - Vitalii Kleshchevnikov
AU - Fabrizio De Rita
AU - David Crossland
AU - Marita Bosticardo
AU - Francesca Pala
AU - Elena Prigmore
AU - Nana-Jane Chipampe
AU - Martin Prete
AU - Lijiang Fei
AU - Ken To
AU - Roger A. Barker
AU - Xiaoling He
AU - Filip Van Nieuwerburgh
AU - Omer Ali Bayraktar
AU - Minal Patel
AU - E. Graham Davies
AU - Muzlifah A. Haniffa
AU - Virginie Uhlmann
AU - Luigi D. Notarangelo
AU - Ronald N. Germain
AU - Andrea J. Radtke
AU - John C. Marioni
AU - Tom Taghon
AU - Sarah A. Teichmann
AB - 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.
BT - Nature
DA - 2024-11
DO - 10.1038/s41586-024-07944-6
IS - 8039
LA - en
N2 - 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.
PY - 2024
SP - 708
EP - 718
T2 - Nature
TI - A spatial human thymus cell atlas mapped to a continuous tissue axis
UR - https://www.nature.com/articles/s41586-024-07944-6
VL - 635
Y2 - 2024-11-26
SN - 1476-4687
ER -