Single-cell transcriptome analysis reveals coordinated ectopic gene-expression patterns in medullary thymic epithelial cells.
Single-cell transcriptome analysis reveals coordinated ectopic gene-expression patterns in medullary thymic epithelial cells.
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DOI：
10.1038/ni.3246
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发表时间：
2015-09
影响因子：
30.5
通讯作者：
Steinmetz LM
中科院分区：
文献类型：
--
作者：
Brennecke P;Reyes A;Pinto S;Rattay K;Nguyen M;Küchler R;Huber W;Kyewski B;Steinmetz LM
胸腺髓质上皮细胞（mTEC）中组织限制性自身抗原（TRA）的表达对于自身耐受诱导和防止自身免疫是必不可少的，每个TRA仅在少数mTEC中表达。这一过程如何在单个mTEC中调节并在群体水平上协调，使得不同的单细胞模式加起来忠实地代表TRAs，目前还知之甚少。在这里，我们使用单细胞RNA测序，并提供了许多反复出现的TRA共表达模式的证据，每种模式仅存在于mTEC的一个子集中。共表达基因在基因组中聚集，并显示出增强的染色质可及性。我们的研究结果表明TRA在mTECs中的表达是一个协调的过程，这可能涉及染色质的局部重建，从而确保了免疫自我的全面代表性。
Expression of tissue-restricted self-antigens (TRAs) in medullary thymic epithelial cells (mTECs) is essential for self-tolerance induction and prevents autoimmunity, with each TRA being expressed in only a few mTECs. How this process is regulated in single mTECs and coordinated at the population level, such that the varied single-cell patterns add up to faithfully represent TRAs, is poorly understood. Here we used single-cell RNA-sequencing and provide evidence for numerous recurring TRA co-expression patterns, each present in only a subset of mTECs. Co-expressed genes clustered in the genome and showed enhanced chromatin accessibility. Our findings characterize TRA expression in mTECs as a coordinated process, which might involve local re-modeling of chromatin and thus ensures a comprehensive representation of the immunological self.