Single-cell sequencing has revealed a more complex array of thymic epithelial cells

• Published in: Immunology letters 2024-10, Vol.269, p.106904, Article 106904
• Main Authors: Pardini, Eleonora, Barachini, Serena, Alì, Greta, Infirri, Gisella Sardo, Burzi, Irene Sofia, Montali, Marina, Petrini, Iacopo
• Format: Article
• Language: English
• Subjects: AIRE; Cortical thymic epithelial cells; Medullary thymic epithelial cells; Thymic epithelial tumors; Thymus
• ISSN: 0165-2478; 1879-0542; 1879-0542
• DOI: 10.1016/j.imlet.2024.106904

•Thymic epithelial cells are divided into cortical (cTEC) and medullary (mTEC) based on their spatial distribution, surface markers, and gene expression patterns.•Single-cell sequencing analysis has revealed novel subpopulations of TECs, particularly within the medullary compartment.•cTECs can be functionally classified into cells that facilitate thymocyte differentiation and those engaged in positive selection.•AIRE and FEZF2 orchestrate the promiscuous gene expression in the thymic medulla, essential for the negative selection of thymocytes.•mTECs are categorized into pre-AIRE cells, which encompass junctional precursors, mature mTECs expressing AIRE, and post-AIRE cells. Thymic epithelial cells participate in the maturation and selection of T lymphocytes. This review explores recent insights from single-cell sequencing regarding classifying thymic epithelial cells in both normal and neoplastic thymus. Cortical thymic epithelial cells facilitate thymocyte differentiation and contribute to positive selection. Medullary epithelial cells are distinguished by their expression of AIRE. Cells progress from a pre-AIRE state, containing precursors with cortical and medullary characteristics, termed junctional cells. Mature medullary epithelial cells exhibit promiscuous gene expression and after that downregulate AIRE mRNA. Post-AIRE cells can adopt a Hassall corpuscle-like phenotype or exhibit distinctive differentiation characteristics including tuft cells, ionocytes, neuroendocrine cells, and myoid cells.