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Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans

  • Sangsin Lee (Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine) ;
  • Seung Geun Song (Department of Pathology, Seoul National University College of Medicine) ;
  • Doo Hyun Chung (Laboratory of Immune Regulation, Department of Biomedical Sciences, Seoul National University College of Medicine)
  • Received : 2023.07.19
  • Accepted : 2023.08.07
  • Published : 2023.10.31
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Abstract

Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.

Keywords

Acknowledgement

This research was supported by National Research Foundation of Korea (NRF) grants funded by the Korean government Ministry of Science and ICT (MSIT) (grant No: NRF-2020R1A2C2008312 and RS-2023-00217571). This study was also supported by grant No. 0320200010 from the SNUH Research Fund.

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