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Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays
Published on: June 9, 2015
Integrative transcriptomic and proteomic profiling reveals altered thymocyte development and microenvironment
Wei Lin1,2, Fuju Sun3, Haitao Pan3
1Tongde Hospital of Zhejiang Province Affiliated to Zhejiang Chinese Medical University (College of Integrated Traditional Chinese and Western Medicine Clinical Medicine), Hangzhou, China.
Frontiers in Cell and Developmental Biology
|July 10, 2026
Summary
Middle-aged mice show thymic involution, with reduced T cells and increased myeloid cells. Integrative omics reveal inflammatory, metabolic, and extracellular matrix remodeling, mirroring human thymus aging.
Area of Science:
- Immunology
- Aging Research
- Molecular Biology
Background:
- Age-related thymic atrophy (ARTA) is a key aspect of immunosenescence.
- The precise developmental checkpoints and molecular drivers of thymic degeneration with age are not fully understood.
Purpose of the Study:
- To investigate the molecular and cellular changes in the thymus during aging.
- To identify early developmental impediments and coordinated molecular programs driving thymic atrophy.
- To assess the translational relevance of mouse findings to human thymus aging.
Main Methods:
- Comparison of young (1-month) and middle-aged (12-month) male ICR mice.
- Analysis included thymus weight, histopathology, peripheral blood counts, and immunostaining.
- RNA-sequencing and proteomics were performed, followed by integrated multi-omics pathway analysis.
- Public human thymus datasets were analyzed for translational relevance.
Main Results:
- Middle-aged mice displayed thymic involution, peripheral lymphopenia, and increased myeloid cells.
- Histopathology showed lipid accumulation, increased apoptosis, and altered thymic architecture.
- Multi-omics revealed suppressed DNA replication and enhanced inflammatory, ECM-receptor interaction, and fatty acid metabolism pathways.
- Human thymus aging showed similar molecular signatures, associated with mesenchymal cells.
Conclusions:
- Aging disrupts early thymocyte differentiation, leading to thymic atrophy.
- Inflammatory responses, ECM remodeling, and metabolic reprogramming characterize aged thymuses.
- Integrative omics data provide targets for interventions to preserve immune homeostasis.
