METHODS: We analyzed single-cell transcriptomic data of peripheral blood mononuclear cells (PBMCs) from healthy individuals, sepsis and septic shock patients, identified differences in gene expression and cell-cell communication between different cell types during disease progression. Moreover, our analyses were further validated with flow cytometry and bulk RNA-seq data.
RESULTS: Our study elucidates the alterations in cellular proportions and cell-cell communication among healthy controls, sepsis, and septic shock patients. We identified a specific augmentation in the Resistin signaling within sepsis monocytes, mediated via RETN-CAP1 ligand-receptor pairs. Additionally, we observed enhanced IL16 signaling within monocytes from septic shock patients, mediated through IL16-CD4 ligand-receptor pairs. Subsequently, we confirmed our findings by validating the increase in CAP-1+ monocytes in sepsis and IL16+ monocytes in septic shock in mouse models. And a significant upregulation of CAP-1 and IL16 was also observed in the bulk RNA-seq data from patients with sepsis and septic shock. Furthermore, we identified four distinct clusters of CD14+ monocytes, highlighting the heterogeneity of monocytes in the progress of sepsis.
CONCLUSIONS: In summary, our work demonstrates changes in cell-cell communication of healthy controls, sepsis and septic shock, confirming that the molecules CAP-1 and IL16 on monocytes may serve as potential diagnostic markers for sepsis and septic shock, respectively. These findings provide new insights for early diagnosis and stratified treatment of the disease.
方法:我们分析了健康个体外周血单核细胞(PBMC)的单细胞转录组数据,脓毒症和脓毒性休克患者,在疾病进展过程中,确定了不同细胞类型之间基因表达和细胞间通讯的差异。此外,我们的分析通过流式细胞术和大量RNA-seq数据进一步验证.
结果:我们的研究阐明了健康对照中细胞比例和细胞间通讯的改变,脓毒症,和脓毒性休克患者。我们发现了败血症单核细胞内抵抗素信号的特异性增强,通过RETN-CAP1配体-受体对介导。此外,我们观察到脓毒性休克患者单核细胞内IL16信号增强,通过IL16-CD4配体-受体对介导。随后,我们通过验证小鼠模型中脓毒症中CAP-1+单核细胞和脓毒性休克中IL16+单核细胞的增加,证实了我们的发现.并且在来自脓毒症和脓毒性休克患者的大量RNA-seq数据中也观察到CAP-1和IL16的显著上调。此外,我们确定了四个不同的CD14+单核细胞簇,强调单核细胞在脓毒症进展中的异质性。
结论:总之,我们的工作证明了健康对照的细胞-细胞通讯的变化,脓毒症和脓毒性休克,证实单核细胞上的分子CAP-1和IL16可以作为脓毒症和脓毒性休克的潜在诊断标志物,分别。这些发现为疾病的早期诊断和分层治疗提供了新的见解。