Abstract
AB034. Single-cell RNA-seq reveals altered gene expression and cellular composition in thymic epithelial cells of type B thymoma
Nobuko Akiyama1,2, Kano Namiki1,2, Kenta Horie1, Takahisa Miyao1, Maki Miyauchi1,2, Mizuki Morota3, Jun Nakajima3, Taishin Akiyama1,2
1Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama, Japan;
2Immunobiology, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan;
3Department of Thoracic Surgery, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
Correspondence to: Taishin Akiyama, PhD. Laboratory for Immune Homeostasis, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan; Immunobiology, Yokohama City University Graduate School of Medical Life Science, Yokohama, Japan. Email: taishin.akiyama@riken.jp.
Background: Thymic epithelial cells (TECs) play a crucial role in thymoma pathogenesis and associated autoimmune conditions. This study aims to elucidate the alterations in gene expression and cellular composition of TECs within type B thymomas, which are often associated with autoimmune diseases.
Methods: We conducted single-cell RNA sequencing (scRNA-seq) on TECs isolated from both tumor and normal regions in type B thymoma patients. Using droplet-based scRNA-seq, we analyzed 15,062 tumor-derived TECs and 16,541 normal TECs from three patients of type B thymoma.
Results: Cell clustering analysis revealed increased cortical TECs (cTECs) and decreased specific subsets of medullary TECs (mTECs) in tumor regions compared to normal regions. Differential gene expression analysis further highlighted distinct transcriptional profiles between TEC subsets from tumor and normal regions. Notably, genes typically expressed in normal cTECs were aberrantly up-regulated in mTEC subsets within the tumor regions. To uncover the underlying mechanisms driving these gene expression changes, we focused on transcription factors differentially expressed in tumor TECs. Based on these insights, we established a mouse model that partially mirrors the gene expression profile observed in thymoma. This model provides a valuable tool for investigating the potential roles of these gene expression changes in thymoma-associated autoimmune diseases.
Conclusions: Our findings underscore the importance of altered TEC subsets and their gene expression profiles in thymoma development and associated autoimmunity, offering new avenues for therapeutic intervention.
Keywords: Thymoma; autoimmunity; thymic epithelial cells (TECs)
Acknowledgments
Funding: This work was supported by Grants-in-Aid for Scientific Research from JSPS (Nos. 20K07332, 20H03441, 23H02708, 23K06385) (T.A., N.A.) and RIKEN Incentive Research Projects (Nos. FY2023, FY2024) (N.A., T.M.), CREST from Japan Science and Technology Agency (No. JPMJCR2011) (T.A.).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://med.amegroups.com/article/view/10.21037/med-24-ab034/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Research Ethics Committee of RIKEN [No. H30-26(6)] and the Research Board of The University of Tokyo Graduate School of Medicine [No. 2018192G-(2)]. Informed consent was obtained from all individual participants.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
doi: 10.21037/med-24-ab034
Cite this abstract as: Akiyama N, Namiki K, Horie K, Miyao T, Miyauchi M, Morota M, Nakajima J, Akiyama T. AB034. Single-cell RNA-seq reveals altered gene expression and cellular composition in thymic epithelial cells of type B thymoma. Mediastinum 2024;8:AB034.
