AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma.
AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma.
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DOI：
10.1002/cam4.5777
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发表时间：
2023-04
期刊：
影响因子：
4
通讯作者：
Oya, Takeshi
中科院分区：
文献类型：
--
作者：
Matsumoto, Minoru;Ohmura, Takuya;Hanibuchi, Yuto;Ichimura-Shimizu, Mayuko;Saijo, Yasuyo;Ogawa, Hirohisa;Miyazawa, Ryuichiro;Morimoto, Junko;Tsuneyama, Koichi;Matsumoto, Mitsuru;Oya, Takeshi
关键词：
尽管胸腺皮质上皮细胞（cTECs）和髓质上皮细胞（mTECs）在生理学上有明显区别，但胸腺癌（TC）和其他胸腺上皮肿瘤的起源细胞仍是个谜。我们通过关注AIRE来解决这个问题，AIRE是一种mTEC特异性转录调节因子，是免疫自我耐受所必需的。免疫组化结果显示，大部分TC表达AIRE，呈典型的核点形态。TCGA‐THYM数据库中的RNA‐seq数据支持TC中的AIRE表达。此外，我们对最近人类胸腺单细胞RNA测序数据的生物信息学方法揭示了TC具有多个mTEC亚群的分子特征。相比之下，TC缺乏cTEC的基因特征。我们提出TC是源自mTEC的肿瘤。起源于胸腺上皮细胞（TEC）的胸腺上皮肿瘤分为六种类型的胸腺瘤（A型、AB型、B1-B3型胸腺瘤和伴有淋巴基质的小结节胸腺瘤[MNT]）和胸腺癌（TC）。尽管在生理学上皮质（cTECs）和髓质TECs（mTECs）之间有明显的区别，但每种泰特的起源细胞仍然是个谜。在目前的研究中，我们证实了AIRE（一种mTEC特异性转录调节因子）在大多数TC中在蛋白质和mRNA水平上的表达。此外，我们的生物信息学方法揭示了TC具有多个mTEC亚群的分子特征，表明它们的细胞起源为mTEC。
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. Thymic epithelial tumors originating from thymic epithelial cells (TECs) are classified into six types of thymomas (Type A, AB, B1‐B3 thymomas, and micronodular thymoma with lymphoid stroma [MNT]) and thymic carcinoma (TC). Despite the clear distinction between cortical (cTECs) and medullary TECs (mTECs) in physiology, the cell of origin of each TET has remained enigmatic. In the current study, we confirmed the expression of AIRE, an mTEC‐specific transcriptional regulator, in most TCs at both protein and mRNA levels. Furthermore, our bioinformatics approach has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations, suggesting their cell of origin as mTECs.
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影响因子：
16.6
作者：
Bautista JL;Cramer NT;Miller CN;Chavez J;Berrios DI;Byrnes LE;Germino J;Ntranos V;Sneddon JB;Burt TD;Gardner JM;Ye CJ;Anderson MS;Parent AV
通讯作者：
Parent AV
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3.5
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Yamamoto, Nobuyuki
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56.9
作者：
Anderson, MS;Venanzi, ES;Mathis, D
通讯作者：
Mathis, D
影响因子：
30.8
作者：
Nagamine, K;Peterson, P;Shimizu, N
通讯作者：
Shimizu, N
影响因子：
4.7
作者：
Kashima J;Hishima T;Okuma Y;Horio H;Ogawa M;Hayashi Y;Horiguchi SI;Motoi T;Ushiku T;Fukayama M
通讯作者：
Fukayama M