Spatial cartography of human thymus enables the geopositioning of lineage transcription factors in rare mimetic thymic epithelial cells

Spatial cartography of human thymus enables the geopositioning of lineage transcription factors in rare mimetic thymic epithelial cells

Nature Communications

10.1038/s41467-026-68596-w

https://doi.org/10.1038/s41467-026-68596-w

Uma S. Kamaraj, Ying Chen, Junjie Lei, Pradeep Gautam, Pongsatorn Horcharoensuk, Czaryna K. M. Clemente, Katja G. Weinacht, Nicholas R. J. Gascoigne, Jinmiao Chen, Ching Kit Chen, Qingfeng Chen, Qi-Jing Li, Lai Guan Ng, Yuin-Han Loh

10 March 2026

Kamaraj, U. S., Chen, Y., Lei, J., Gautam, P., Horcharoensuk, P., Clemente, C. K. M., Weinacht, K. G., Gascoigne, N. R. J., Chen, J., Chen, C. K., Chen, Q., Li, Q.-J., Ng, L. G., & Loh, Y.-H. (2026). Spatial cartography of human thymus enables the geopositioning of lineage transcription factors in rare mimetic thymic epithelial cells. Nature Communications. https://doi.org/10.1038/s41467-026-68596-w

The thymus is the primary site for T cell maturation. While transcriptional profiling of human thymi has been reported, a high-resolution spatial atlas is needed. Here we use Stereo-seq spatial transcriptomics to generate a spatial atlas of the human fetal (13, 14, 17 or 18 weeks post-conception) and pediatric (7 weeks, and 2, 5 or 6 years old) thymi. The architecture of the thymus comprises regions such as the outer cortex, inner medulla, and septa, and contains multiple cell types, including thymic epithelial cells (TEC), thymocytes, dendritic cells, macrophages, and B cells. Utilising this spatial transcriptomics and proteomics information, we further describe lineage-defining transcription factors (TF) that govern molecular signatures of rare mimetic TEC regulation. Our study thus establishes a high-resolution spatial atlas of the human fetal and pediatric thymi to uncover distinct architectural features and TFs regulating these rare cell types, and serves as a resource for further studies.

Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

This research / project is supported by the National Research Foundation - NRF Investigatorship award
Grant Reference no. : NRFI2018-02

This research / project is supported by the National Medical Research Council - Open Fund - Individual Research Grant
Grant Reference no. : OFIRG21nov-0088

This research / project is supported by the Singapore Food Agency and the Agency for Science, Technology and Research - Singapore Food Story (SFS) R&D Programme
Grant Reference no. : W22W3D0007

This research / project is supported by the National Research Foundation - Competitive Research Programme
Grant Reference no. : CRP29-2022-0005

This research / project is supported by the A*STAR Biomedical Research Council, Central Research Fund, - Use-Inspired Basic Research
Grant Reference no. : CRF UIBR

This research / project is supported by the A*STAR - Industry Alignment Fund Prepositioning Programme IAF-PP
Grant Reference no. : H23J2a0095

This research / project is supported by the A*STAR - Industry Alignment Fund Prepositioning Programme IAF-PP
Grant Reference no. : H23J2a0097

This research / project is supported by the Singapore Ministry of Education grant - Singapore Ministry of Education grant
Grant Reference no. : MOE-000112

https://oar.a-star.edu.sg/communities-collections/articles/22999

2041-1723

Institute of Molecular and Cell Biology

https://doi.org/10.1038/s41467-026-68596-w