Mapping murine thymic epithelial cells: functional ultrastructure and implications for thymopoiesis.

Abstract

We present a novel classification system for murine thymic epithelial cells (TECs), identifying 11 distinct types, four in the thymic cortex and seven in the medulla, based on their spatial localization and unique ultrastructural features. As key stromal components of the thymic microenvironment, TECs play indispensable roles in T cell development, including thymocyte selection, antigen presentation, and structural support. Our classification spans from the subcapsular cortex to the deep medulla and incorporates microanatomical context, morphology, and functional characteristics, providing a comprehensive and flexible framework to study TEC heterogeneity in relation to thymopoiesis. Aligning with TEC classification in rats and humans, this system highlights conserved spatial organization across species while remaining adaptable for refinement. Each TEC type is distinguished by features such as chromatin organization, cytoplasmic morphology, vacuolar content, and organelle distribution, attributes that suggest distinct functional contributions to various stages of thymocyte maturation. Importantly, the classification is designed for logical expansion both horizontally (inclusion of additional subtypes within the proposed TEC types) and vertically (inclusion of entirely novel TEC types). By integrating detailed morphological observations with testable functional hypotheses, this framework underscores the essential role of TEC diversity in supporting thymic architecture and orchestrating effective T cell output. Overall, it offers a robust foundation for future research into immune development and the pathological consequences of thymic dysfunction.