摘要： 目的·探索人类胸腺基质细胞在不同发育阶段的转录动态。方法·利用人类胸腺单细胞转录组数据E-MATB-8581，借助蛋白质相互作用数据库分析不同类型胸腺基质细胞在胚胎期、婴儿期和成人期的分群特点，并计算基因表达差异，结合富集分析推测它们功能变化。结果·相比于树突状细胞，胸腺上皮细胞（thymic epithelial cell，TEC）、内皮细胞（endothelial cell，Endo）和成纤维细胞（fibroblast，Fb）由不同发育阶段造成的基因表达差异更为显著。Ⅰ型髓质TEC（medullary TEC，mTEC）细胞在成年期的抗原提呈功能下降，主要组织相容性复合物（major histocompatibility complex，MHC）Ⅱ类分子表达下调。在出生后的胸腺中，Fb逐渐富集参与T细胞抗原识别、分化和激活的功能。在胚胎期和婴儿期，Endo上调表达的基因主要富集与细胞外基质等相关的通路，而出生后则富集抗原提呈相关通路，并上调2类MHC分子的表达。结论·生物信息学方法揭示了mTEC、Fb和Endo是易受胸腺发育和退化影响的细胞类型。人类胸腺生理性退化可能主要影响T细胞分化中的阴性选择。
关键词: 胸腺基质细胞, 发育, 阴性选择, 单细胞RNA测序, 基因表达 Abstract: Objective·To explore the transcriptomic dynamics of human thymic stroma cells across different developmental stages.
Methods·The single-cell transcriptome datasets of human thymus were downloaded from ArrayExpress (E-MATB-8581). The cellular maps of thymic stroma cells across different developmental stages were analyzed based on protein-protein interaction. The differentially expressed genes of fetal, infant and adult stages were calculated. The cell state alternation across different developmental stages was predicted based on functional enrichment analysis.
Results·The transcriptomic dynamics of thymic epithelial cells (TEC), endothelial cells (Endo) and fibroblasts (Fb) were more remarkable compared with dendritic cells. In adult thymus, there was decline of antigen presenting function and down-regulation of major histocompatibility complex (MHC) class Ⅱ genes in medullary TEC type Ⅰ cells. The fibroblasts enriched functions related to antigen recognition, differentiation and activation of T cells in postnatal thymus. The up-regulated genes of thymic Endo enriched functions such as extracellular matrix during fetal and infant stages, while up-regulated MHC genes and enriched pathways associated with antigen presenting in adult thymus.
Conclusion·Bioinformatics analysis revealed that mTEC, Fb and Endo were the susceptible stroma cell types in response to thymic development and senescence. The involution of human thymus may affect the negative selection of T cell differentiation mostly.
Key words: thymic stroma, development, negative selection, single-cell RNA-sequencing, gene expression PDF全文下载地址:
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