Abstract
The human thymus plays a key role in the development of the adaptive immune system. Its development and pathologic aberrations with missing involution occupy the scientific world for years. Here, we present a comprehensive single-cell RNA sequencing (scRNA-seq) analysis of 453,727 cells across 53 datasets derived from healthy prenatal, pediatric, and adult thymic tissues, as well as six pathological conditions, including thymic hyperplasia and thymic epithelial tumors (types A, AB, B, C, and micronodular thymoma). We created a high-resolution cellular atlas revealing disease-specific cellular populations and transcriptional programs, particularly within fibroblast subsets and thymic epithelial cells. Comparative analysis uncovers distinct intercellular communication patterns and identifies transcriptional alterations associated with thymic pathology. Integration with published bulk RNA-seq datasets supports the robustness and translational relevance of our findings. This study provides a foundational resource for understanding the cellular and molecular landscape of thymic development and disease, offering avenues for diagnostic and therapeutic innovations.
Similar content being viewed by others
Acknowledgements
We would like to thank Dr. HP Haselsteiner and the CRISCAR Familienstiftung for their support and belief in the Medical University/Aposcience AG public-private partnership. The authors additionally acknowledge the core facilities of the Medical University of Vienna, a member of Vienna Life Science Instruments. Some of the computational results presented were achieved using the Vienna Scientific Cluster (VSC). H.J.A. discloses support for the research and publication of this work from the FFG Grant “APOSEC” (852748 and 862068; 2015-2019), the Vienna Business Agency “APOSEC to clinic” (ID 2343727, 2018-2020), and Aposcience AG. M.M. discloses support for the research and publication of this work from the Federal Ministry of Women, Science and Research, Republic of Austria, and the Austrian Science Fund (Grant-https://doi.org/10.55776/PAT8996524).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Source data
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
About this article
Cite this article
Direder, M., Wielscher, M., Salek, M. et al. A single-cell atlas revealing cellular heterogeneity across healthy and diseased human thymus. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72760-7
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41467-026-72760-7
