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单细胞RNA测序与批量RNA测序的综合分析揭示了接受静脉-动脉体外膜肺氧合支持的心源性休克患者在静脉-动脉体外膜肺氧合建立前采集的外周血单个核细胞的预后标志物。

Integrative Analyses of Single-Cell RNA-Sequencing and Bulk RNA-Sequencing Reveal Prognostic Markers of Peripheral Blood Mononuclear Cells in Patients with Cardiogenic Shock Receiving Venous-Arterial Extracorporeal Membrane Oxygenation Support Collected before Venous-Arterial Extracorporeal Membrane Oxygenation Establishment.

作者信息

Wang Lei, Zhong Guodong, Chen Liangwan

机构信息

Department of Cardiovascular Surgery, Fujian Medical University Union Hospital, Fuzhou 350000, China.

Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou 350000, China.

出版信息

ACS Omega. 2024 Dec 31;10(1):637-654. doi: 10.1021/acsomega.4c07339. eCollection 2025 Jan 14.

DOI:10.1021/acsomega.4c07339
PMID:39829552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11739955/
Abstract

The impact of changes in peripheral blood mononuclear cells (PBMCs) on the prognosis of patients with cardiogenic shock (CS) receiving venous-arterial extracorporeal membrane oxygenation (VA-ECMO) remains unclear. A single-cell RNA-sequencing (scRNA-seq) and a bulk RNA-sequencing (bulk RNA-seq) data sets of pre-ECMO PBMCs of CS patients were obtained from the gene expression omnibus database, which were analyzed using the "Seurat" and "limma" packages, respectively. The counts of different PMBC cell types, differential expression genes (DEGs), pathway enrichment analysis, cell-cell communication analysis, pseudotime analysis, and immune cell infiltration analysis were compared between VA-ECMO groups with different prognoses. The intersectional DEGs of the two data sets were screened. PBMCs were collected from VA-ECMO patients for experimental verification. For scRNA-seq analysis, ten kinds of PBMCs were identified, and B and NK/NKT cells which had significant differences in cell counts across groups were further divided into four subsets. The counts of B and NK/NKT cells with high expression levels of HSPA1B were higher in the poor-prognosis group, which was consistent with the bulk RNA-seq analysis. Pseudotime analysis also indicated that B-HSPA1B cells gradually increased in the poor-prognosis group. HSPA1B was found to be the intersectional upregulated DEG in both data sets, which was consistent with the experimental verification using clinical samples. The increased counts of B and NK/NKT cells as well as high expression levels of HSPA1B in these cell types or in the total pre-ECMO PBMCs were predictors of poor prognosis.

摘要

外周血单个核细胞(PBMCs)的变化对接受静脉-动脉体外膜肺氧合(VA-ECMO)的心源性休克(CS)患者预后的影响尚不清楚。从基因表达综合数据库中获取CS患者ECMO前PBMCs的单细胞RNA测序(scRNA-seq)和批量RNA测序(bulk RNA-seq)数据集,分别使用“Seurat”和“limma”软件包进行分析。比较不同预后的VA-ECMO组之间不同PMBC细胞类型的计数、差异表达基因(DEGs)、通路富集分析、细胞间通讯分析、拟时间分析和免疫细胞浸润分析。筛选两个数据集的交叉DEGs。从VA-ECMO患者中收集PBMCs进行实验验证。对于scRNA-seq分析,鉴定出十种PBMCs,并且在各组细胞计数上有显著差异的B细胞和NK/NKT细胞进一步分为四个亚群。预后较差组中HSPA1B高表达的B细胞和NK/NKT细胞计数较高,这与批量RNA-seq分析结果一致。拟时间分析还表明,预后较差组中B-HSPA1B细胞逐渐增加。发现HSPA1B是两个数据集中交叉上调的DEG,这与使用临床样本的实验验证结果一致。这些细胞类型或ECMO前PBMCs总数中B细胞和NK/NKT细胞计数增加以及HSPA1B高表达是预后不良的预测指标。

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