Department of Molecular Pathology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
Division of Molecular Immunology, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
Cancer Med. 2023 Apr;12(8):9843-9848. doi: 10.1002/cam4.5777. Epub 2023 Mar 13.
Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA-seq data in the TCGA-THYM database. Furthermore, our bioinformatics approach to the recent single-cell RNA-seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs.
尽管在生理学上皮质胸腺上皮细胞 (cTECs) 和骨髓胸腺上皮细胞 (mTECs) 之间有明显的区别，但胸腺癌 (TCs) 和其他胸腺癌的起源细胞仍然是个谜。我们通过关注 mTEC 特异性转录调节剂 AIRE 来解决这个问题，AIRE 是免疫自身耐受所必需的。我们发现，通过免疫组织化学，大多数 TCs 表达具有典型核点形态的 AIRE。TCGA-THYM 数据库中的 RNA-seq 数据支持 TCs 中 AIRE 的表达。此外，我们对最近人类胸腺单细胞 RNA-seq 数据的计算生物学方法揭示了 TCs 具有多个 mTEC 亚群的分子特征。相比之下，TCs 缺乏 cTEC 的基因特征。我们提出 TCs 是源自 mTECs 的肿瘤。
