ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2024, Vol. 33 ›› Issue (2): 127-135.DOI: 10.3969/j.issn.1006-298X.2024.02.005

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单细胞RNA测序揭示维持性血液透析患者外周血免疫细胞的转录组特征

  

  • 出版日期:2024-04-28 发布日期:2024-04-23

Single-cell RNA sequencing reveals distinct immune cell subsets and signaling pathways in maintenance hemodialysis patients

  • Online:2024-04-28 Published:2024-04-23

摘要: 目的:通过单细胞RNA测序(scRNA-seq)揭示维持性血液透析(MHD)患者的外周血单个核细胞(PBMC)的转录组特征及免疫状态。
方法:使用scRNA-seq技术对MHD患者PBMC进行了研究,揭示其在相关疾病中的状态及分子特性的变化。采用无监督聚类和注释分析对PBMC进行了分类和鉴别,对主要细胞类型进行了差异基因富集和细胞间通讯分析。同时,通过分析代谢组学数据集和临床实验室指标进行进一步验证。
结果:成功建立了MHD患者PBMC的转录组图谱,鉴定了8种主要细胞类型。通过与健康对照组进行差异基因功能富集分析,发现MHD患者的淋巴细胞和单核细胞炎症相关通路富集评分显著上升,B淋巴细胞的脂质代谢通路富集评分下降,而单核细胞的脂质通路富集评分则呈上升趋势。细胞通讯结果显示,T细胞和单核细胞在多种信号通路中扮演着发送者和接收者的角色。此外,代谢组学分析表明,患者外周血中脂质代谢产物增多。临床实验室结果进一步验证了患者存在较高的炎症和脂质水平。
结论:scRNA-seq揭示MHD患者外周循环血液中长期伴有免疫失调、慢性炎症及脂质代谢的紊乱。


关键词: 单细胞RNA测序, 维持性血液透析, 单个核细胞, 脂质代谢

Abstract: Objective:This study aimed to elucidate the transcriptomic features and immune status of peripheral blood mononuclear cells (PBMC) in maintenance hemodialysis (MHD) patients using single-cell RNA sequencing (scRNA-seq) technology.
Methodology:We conducted a study using scRNA-seq technology to analyze single nuclear cells in the peripheral blood of MHD-treated patients, revealing their status and molecular characteristics in relevant diseases. Unsupervised clustering and annotation analysis were employed to classify and identify individual PBMCs, followed by differential gene enrichment and intercellular communication analysis of major cell types. Furthermore, validation was performed through analysis of metabolomic datasets and clinical laboratory indicators.
Results:We successfully established a transcriptomic atlas of PBMCs from MHD patients, identifying eight major cell types. Differential gene functional enrichment analysis between MHD patients and healthy controls revealed a significant increase in inflammation-related pathway enrichment scores in lymphocytes and monocytes. Meanwhile, B lymphocytes showed a decrease in lipid metabolism pathway enrichment scores, while monocytes exhibited an increasing trend in lipid pathway enrichment scores. Cell communication analysis indicated that T cells and monocytes play roles as both senders and receivers in multiple signaling pathways. Additionally, metabolomic analysis demonstrated an increase in lipid metabolism products in the peripheral blood of MHD patients. Clinical laboratory results further validated the presence of higher inflammation and lipid levels in these patients.
Conclusion:Single-cell RNA sequencing technology reveals long-term immune dysregulation, chronic inflammation, and disrupted lipid metabolism in the peripheral circulation of maintenance hemodialysis patients.


Key words: single-cell RNA sequencing, maintenance hemodialysis, mononuclear cells, lipid metabolism