Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis.As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area.To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC singlecell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with agerelated TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.

Although more than 90% of melanomas have cutaneous origins, melanomas sometimes present metastatically with no apparent primary lesion. A 62-year-old female presented with black pigmentation on her left thumbnail that had begun 2 years earlier and after the biopsy, she was diagnosed with malignant melanoma. Interestingly, 7 years earlier, a 4 cm palpable mass on her left axilla had been diagnosed as melanoma from an unknown primary site (MUP) with the involvement of an axillary lymph node. We speculate that the melanoma of the left thumb was the primary site and the melanoma in the axilla was a metastasis from the left thumb, and suggest several hypotheses explaining the appearance of the primary lesion as acral lentiginous melanoma after detecting a metastatic site. We consider this case interesting because it helps us to understand the pathogenesis of MUP and reminds physicians to conduct careful periodical work-ups of melanoma patients, and highlights the importance of continued long-term follow-up, especially for patients with MUP.
Axilla ; Biopsy ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; Melanoma ; Middle Aged ; Neoplasm Metastasis ; Pigmentation ; Thumb