老年小鼠和人胸腺上皮细胞的综合转录组学分析。

IF 4.3 4区 医学 Q2 IMMUNOLOGY Immune Network Pub Date : 2023-08-21 eCollection Date: 2023-10-01 DOI:10.4110/in.2023.23.e36
Sangsin Lee, Seung Geun Song, Doo Hyun Chung
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引用次数: 0

摘要

胸腺上皮细胞(TECs)在胸腺发育和胸腺生成中起着关键作用。随着个体年龄的增长,tec经历各种影响其功能的变化,导致细胞数量减少和胸腺选择受损。这些与年龄相关的变化在老鼠和人类身上都观察到了。然而,与年龄相关的TEC功能障碍的确切机制尚不清楚。此外,在这一领域缺乏将小鼠和人类生物过程联系起来的全面研究。为了解决这一差距,我们对小鼠中年轻和年老的TEC进行了广泛的转录组分析,并辅以对公开可用的人类TEC单细胞RNA测序数据的进一步分析。我们的分析揭示了已知和未知通路的改变可能导致与年龄相关的TEC功能障碍。具体来说,我们观察到老年tec中与细胞增殖、T细胞发育、代谢和细胞因子信号通路相关的下调。相反,TGF-β、BMP和Wnt信号通路上调,已知这些信号通路与年龄相关的TEC功能障碍有关或本研究新发现。重要的是,我们发现小鼠tec中这些与年龄相关的变化也始终存在于人类tec中。这种跨物种验证进一步加强了我们发现的意义。总之,我们的综合分析为小鼠和人类老年tec的生物学和免疫学特性提供了有价值的见解。这些发现有助于更好地理解胸腺退化和年龄诱导的免疫功能障碍。
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Comprehensive Transcriptomic Analysis for Thymic Epithelial Cells of Aged Mice and Humans.

Thymic epithelial cells (TECs) play a critical role in thymic development and thymopoiesis. As individuals age, TECs undergo various changes that impact their functions, leading to a reduction in cell numbers and impaired thymic selection. These age-related alterations have been observed in both mice and humans. However, the precise mechanisms underlying age-related TEC dysfunction remain unclear. Furthermore, there is a lack of a comprehensive study that connects mouse and human biological processes in this area. To address this gap, we conducted an extensive transcriptome analysis of young and old TECs in mice, complemented by further analysis of publicly available human TEC single-cell RNA sequencing data. Our analysis revealed alterations in both known and unknown pathways that potentially contribute to age-related TEC dysfunction. Specifically, we observed downregulation of pathways related to cell proliferation, T cell development, metabolism, and cytokine signaling in old age TECs. Conversely, TGF-β, BMP, and Wnt signaling pathways were upregulated, which have been known to be associated with age-related TEC dysfunctions or newly discovered in this study. Importantly, we found that these age-related changes in mouse TECs were consistently present in human TECs as well. This cross-species validation further strengthens the significance of our findings. In conclusion, our comprehensive analysis provides valuable insight into the biological and immunological characteristics of aged TECs in both mice and humans. These findings contribute to a better understanding of thymic involution and age-induced immune dysfunction.

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来源期刊
Immune Network
Immune Network Immunology and Microbiology-Immunology
CiteScore
2.90
自引率
3.30%
发文量
36
期刊介绍: Immune Network publishes novel findings in basic and clinical immunology and aims to provide a medium through which researchers in various fields of immunology can share and connect. The journal focuses on advances and insights into the regulation of the immune system and the immunological mechanisms of various diseases. Research that provides integrated insights into translational immunology is given preference for publication. All submissions are evaluated based on originality, quality, clarity, and brevity
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