Sex biased human thymic architecture guides T cell development through spatially defined niches

Stankiewicz, L. N.; Rossi, F. M.; Zandstra, P. W.; Salim, K.; Flaschner, E. A.; Wang, Y. X.; Edgar, J. M.; Lin, B. Z.; Bingham, G. C.; Major, M. C.; Jones, R. D.; Blau, H.; Rideout, E.; Levings, M. K.

doi:10.1101/2023.04.13.536804

bioRxiv · 10.1101/2023.04.13.536804

Sex biased human thymic architecture guides T cell development through spatially defined niches

Stankiewicz, L. N.·Rossi, F. M.·Zandstra, P. W.·Salim, K.·Flaschner, E. A.·Wang, Y. X.·Edgar, J. M.·Lin, B. Z.·Bingham, G. C.·Major, M. C.·Jones, R. D.·Blau, H.·Rideout, E.·Levings, M. K.

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Abstract

Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a holistic, spatially defined map of tissue niches guiding postnatal T cell development we employed the multidimensional imaging platform CO-detection by indEXing (CODEX), as well as CITE-seq and ATAC-seq. We generated age-matched 4-5-month-old postnatal thymus datasets for male and female donors, and identify significant sex differences in both T cell and thymus biology. We demonstrate a crucial role for JAG ligands in directing thymic-like dendritic cell development, reveal important functions of a novel population of ECM- fibroblasts, and characterize the medullary niches surrounding Hassalls corpuscles. Together, these data represent a unique age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, and provide an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.

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Stankiewicz, L. N., Rossi, F. M., Zandstra, P. W., Salim, K., Flaschner, E. A., Wang, Y. X., Edgar, J. M., Lin, B. Z., Bingham, G. C., Major, M. C., Jones, R. D., Blau, H., Rideout, E., Levings, M. K.. 2023-04-16. Sex biased human thymic architecture guides T cell development through spatially defined niches. https://doi.org/10.1101/2023.04.13.536804

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