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冠心病患者外周血单个核细胞的单细胞 RNA 测序图谱。

Single-cell RNA sequencing atlas of peripheral blood mononuclear cells from subjects with coronary artery disease.

机构信息

Department of Cardiovascular Medicine, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng 224000, Jiangsu Province, China.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

出版信息

Biochim Biophys Acta Mol Cell Res. 2024 Jan;1871(1):119593. doi: 10.1016/j.bbamcr.2023.119593. Epub 2023 Sep 18.

DOI:10.1016/j.bbamcr.2023.119593
PMID:37730128
Abstract

BACKGROUND

The landscape of specific peripheral circulating immune cell subsets at the single-cell level in the occurrence and development of coronary artery disease (CAD) remains poorly understood.

METHODS

We conducted single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from subjects with CAD (n = 3), and controls (n = 3), as well as downstream analysis including cell- and gene-level approaches. This explored the characteristics of peripheral circulating immune cells between CADs and controls by means of Uniform manifold approximation and projection (UMAP), Monocle3 package, CellPhoneDB, and single-cell regulatory network inference and clustering (SCENIC). PBMCs were used as clinical samples for validating our findings by qRT-PCR.

RESULTS

We identified 33 cell clusters among 67,447 cells, including monocytes, T cells, B cells, NK cells, and platelets. The significant difference in the abundance of the 33 clusters of cell type between CADs group and controls group was not found. The JUN was shared in cluster 0, 11,13, and 24 from differential expression genes analysis and SCENIC analysis in monocyte clusters between CAD and controls. Besides, JUN was validated to be significantly upregulated in the CAD group (p = 0.018) and may act as a potential diagnostic biomarker and independent predictor of CAD.

CONCLUSIONS

Our study offered a detailed profiling of single-cell RNA sequencing of PBMCs from subjects with CADs and controls. These data provide a line of evidence that the JUN signaling pathway may be a potential diagnostic and therapeutic molecule target for CAD.

摘要

背景

在冠状动脉疾病(CAD)的发生和发展过程中,特定外周循环免疫细胞亚群在单细胞水平上的特征尚不清楚。

方法

我们对 CAD 患者(n=3)和对照组(n=3)的外周血单个核细胞(PBMCs)进行了单细胞 RNA 测序(scRNA-seq),并进行了包括细胞和基因水平的下游分析。通过统一流形逼近和投影(UMAP)、Monocle3 包、CellPhoneDB 和单细胞调控网络推断和聚类(SCENIC),我们探索了 CAD 和对照组之间外周循环免疫细胞的特征。使用 PBMC 作为临床样本,通过 qRT-PCR 验证我们的发现。

结果

我们在 67447 个细胞中鉴定出 33 个细胞簇,包括单核细胞、T 细胞、B 细胞、NK 细胞和血小板。在 CAD 组和对照组之间,33 个细胞簇的细胞类型丰度没有显著差异。在单核细胞簇中,从差异表达基因分析和 CAD 与对照组之间的 SCENIC 分析中,JUN 共享簇 0、11、13 和 24。此外,JUN 在 CAD 组中被验证为显著上调(p=0.018),可能作为 CAD 的潜在诊断生物标志物和独立预测因子。

结论

我们的研究提供了 CAD 患者和对照组 PBMCs 的单细胞 RNA 测序的详细分析。这些数据提供了证据表明,JUN 信号通路可能是 CAD 的潜在诊断和治疗分子靶标。

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