EGAS00001004311-2-sc-2024-07-09T11:42:46Z - samples

T cells develop from circulating precursor cells, which enter the thymus and migrate
through specialised sub-compartments that support their maturation and selection. In
humans, this process starts in early fetal development and is highly active until
thymic involution in adolescence. To map the micro-anatomical underpinnings of this
process in pre- and early postnatal stages, we established a novel quantitative
morphological framework for the thymus, the Cortico-Medullary Axis, and used it to
perform a spatially resolved analysis. 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 within the first
trimester of fetal development. We pinpoint tissue niches of thymic epithelial cell
progenitors and distinct subtypes associated with Hassall’s corpuscles and uncover
divergence in the timing of medullary entry between CD4 vs. 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 Organ Axis construction (TissueTag), which can be
applied to any tissue.EGA dataset EGAD00001015384