Autoimmune regulator⁺ (Aire) medullary thymic epithelial cells (mTECs) play a critical role in tolerance induction. Several studies demonstrated that Aire⁺mTECs differentiate further into Post‐Aire cells. Yet, the identification of terminal stages of mTEC maturation depends on unique fate‐mapping mouse models. Herein, we resolve this limitation by segmenting the mTEC^hi(MHCII^hiCD80^hi) compartment into mTEC^A/hi (CD24⁻Sca1⁻), mTEC^B/hi (CD24⁺Sca1⁻), and mTEC^C/hi (CD24⁺Sca1⁺). While mTEC^A/hi included mostly Aire‐expressing cells, mTEC^B/hi contained Aire⁺ and Aire⁻ cells and mTEC^C/hi were mainly composed of cells lacking Aire. The differential expression pattern of Aire led us to investigate the precursor‐product relationship between these subsets. Strikingly, transcriptomic analysis of mTEC^A/hi, mTEC^B/hi, and mTEC^C/hi sequentially mirrored the specific genetic program of Early‐, Late‐ and Post‐Aire mTECs. Corroborating their Post‐Aire nature, mTEC^C/hi downregulated the expression of tissue‐restricted antigens, acquired traits of differentiated keratinocytes, and were absent in Aire‐deficient mice. Collectively, our findings reveal a new and simple blueprint to survey late stages of mTEC differentiation.

中文翻译：

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一种鉴定髓质胸腺上皮细胞分化的 Post-Aire 阶段的新方法

自身免疫调节剂⁺ (Aire) 髓质胸腺上皮细胞 (mTECs) 在耐受诱导中起关键作用。几项研究表明，Aire ⁺ mTECs 进一步分化为 Post-Aire 细胞。然而，mTEC 成熟的终末阶段的识别取决于独特的命运映射小鼠模型。在这里，我们通过将 mTEC ^hi (MHCII ^hi CD80 ^hi ) 隔室分割成 mTEC ^A/hi (CD24 ^- Sca1 ^- )、mTEC ^B/hi (CD24 ⁺ Sca1 ^- ) 和 mTEC ^C/hi (CD24 ⁺ Sca1 ⁺）。mTEC ^A/hi主要包括表达 Aire 的细胞，mTEC ^B/hi包含 Aire ⁺和 Aire ^-细胞，mTEC ^C/hi主要由缺乏 Aire 的细胞组成。Aire 的差异表达模式使我们研究了这些子集之间的前体-产物关系。引人注目的是，mTEC ^A/hi、mTEC ^B/hi和 mTEC ^C/hi的转录组分析依次反映了 Early-、 Late- 和 Post-Aire mTEC 的特定遗传程序。证实它们的后 Aire 特性，mTEC ^C/hi下调组织限制性抗原的表达，获得分化角质形成细胞的特征，并且在 Aire 缺陷小鼠中不存在。总的来说，我们的研究结果揭示了一个新的简单蓝图来调查 mTEC 分化的晚期阶段。