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To map the micro-anatomical underpinnings of this process in pre- vs. post-natal states, we undertook a spatially resolved analysis and established a new quantitative morphological framework for the thymus, the Cortico-Medullary Axis. Using this axis in conjunction with the curation of a multimodal single-cell, spatial transcriptomics and high-resolution multiplex imaging atlas, we show that canonical thymocyte trajectories and thymic epithelial cells are highly organised and fully established by post-conception week 12, pinpoint TEC progenitor states, find that TEC subsets and peripheral tissue genes are associated with Hassall\u2019s Corpuscles and uncover divergence in the pace and drivers of medullary entry between CD4 vs. CD8 T cell lineages. These findings are complemented with a holistic toolkit for spatial analysis and annotation, providing a basis for a detailed understanding of T lymphocyte development.<\/jats:p>","DOI":"10.1101\/2023.10.25.562925","type":"posted-content","created":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T16:30:10Z","timestamp":1698510610000},"source":"Crossref","is-referenced-by-count":11,"title":["A spatial human thymus cell atlas mapped to a continuous tissue axis"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7034-0524","authenticated-orcid":false,"given":"Nadav","family":"Yayon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6563-0829","authenticated-orcid":false,"given":"Veronika 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