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Spatial Single-cell Transcriptome Atlas of Mouse Thymus Reveals the T Lymphocyte Dynamics During Development
Jiahao Zhang1,2, Huaiyuan Cai1, Chuanyuan Lu1
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Genomics, Proteomics & Bioinformatics
|March 1, 2026
Summary
This study maps mouse thymus cell types across development, revealing dynamic changes and interactions. It identifies key molecular regulators and highlights autoimmune gene enrichment in specific T cell populations during aging.
Area of Science:
- Immunology
- Developmental Biology
- Genomics
Background:
- The thymus is vital for lymphocyte development but its age-related molecular changes are poorly understood.
- Understanding thymic involution is crucial for comprehending immune system aging and function.
Purpose of the Study:
- To create a comprehensive single-cell transcriptomic resource of the mouse thymus across four developmental stages.
- To investigate dynamic changes in thymic cell composition, transcriptional profiles, and cell-cell interactions during aging.
- To identify molecular regulators and gene expression patterns associated with thymic involution and autoimmune diseases.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of mouse thymus at 3, 9, 15, and 33 weeks.
- Bioinformatic analysis to identify immune cell types, transcriptional dynamics, and spatial relationships.
- Spatial transcriptomics and trajectory analysis to map cell development and interactions.
Main Results:
- Eleven major immune cell types were identified, with dynamic shifts in composition and gene expression over time.
- Thymic involution showed decreased CD8+ T cells and altered expression of Smad4 and Smad7.
- Spatial analysis revealed distinct clustering of DP-2 and DP-3 cells, with MHC-II pathway-mediated interactions between dendritic cells and DP-2 cells.
- Autoimmune disease risk genes were enriched in CD4+ and NKT cells with specific age-related expression patterns.
Conclusions:
- This study provides a valuable single-cell atlas of the mouse thymus, detailing its architecture and immune cell development across ages.
- The findings offer insights into the molecular mechanisms underlying thymic involution and age-related immune changes.
- The resource facilitates further research into thymic function, T cell differentiation, and the genetic basis of autoimmune diseases.
