Luo Xiao-Ting, Hu Hui-Rong, Sun Zhen-Dong, Zhang Li-Hong, Li Yan
Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China.
Front Cell Infect Microbiol. 2025 Mar 6;15:1531125. doi: 10.3389/fcimb.2025.1531125. eCollection 2025.
Monocytes represent a vital cellular subpopulation in the peripheral blood, crucial in the progression of sepsis. Nonetheless, the prognostic role and precise function of monocytes in sepsis are still inadequately understood.
Single-cell transcriptomic sequencing and bioinformatics analysis were performed on peripheral blood samples from septic patients to identify key molecules in cell subsets. Subsequently, the expression pattern of this molecule was validated through diverse biological experiments, encompassing quantitative RT-PCR, western blotting, and immunofluorescence. Finally, the functionality of this molecule was evaluated using its specific agonist.
A total of 22 monocytes-related biomarkers were identified from single-cell and bulk RNA-seq analyses. Initially, LASSO analysis was performed to derive a prognostic signature composed of 4 key genes, including , , and . Subsequently, mendelian randomization and survival analysis demonstrated that only showed crucially protective role in sepsis development and prognosis. Next, was confirmed to be lower expressed in peripheral monocytes of septic patients. Inflammatory markers ( < 0.05) and migration ability of LPS-activated monocytes were significantly reduced after agonist. In addition, agonist decreased the pulmonary tissue monocyte/macrophages infiltration in septic mice.
Monocyte marker represent a promising target for the diagnosis and prognosis evaluation of sepsis and plays a critical role in monocytes activation, tissue inflammatory response and macrophages infiltration. Thus, agonist probably serves as new drug for clinical protection against sepsis.
单核细胞是外周血中重要的细胞亚群，在脓毒症进展中起关键作用。然而，单核细胞在脓毒症中的预后作用和确切功能仍未得到充分了解。
对脓毒症患者的外周血样本进行单细胞转录组测序和生物信息学分析，以确定细胞亚群中的关键分子。随后，通过多种生物学实验验证该分子的表达模式，包括定量逆转录聚合酶链反应、蛋白质印迹法和免疫荧光。最后，使用其特异性激动剂评估该分子的功能。
通过单细胞和批量RNA测序分析共鉴定出22个与单核细胞相关的生物标志物。最初，进行LASSO分析以得出由4个关键基因组成的预后特征，包括 、 、 和 。随后，孟德尔随机化和生存分析表明，只有 在脓毒症的发生和预后中显示出至关重要的保护作用。接下来，证实脓毒症患者外周单核细胞中 的表达较低。 激动剂作用后，LPS激活的单核细胞的炎症标志物（ < 0.05）和迁移能力显著降低。此外， 激动剂减少了脓毒症小鼠肺组织中单核细胞/巨噬细胞的浸润。
单核细胞标志物 是脓毒症诊断和预后评估的一个有前景的靶点，在单核细胞激活、组织炎症反应和巨噬细胞浸润中起关键作用。因此， 激动剂可能作为临床预防脓毒症的新药。
