致命脓毒症期间人类单细胞转录特征的动态变化,Journal of Leukocyte Biology

当前位置： X-MOL 学术 › J. Leukoc. Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

致命脓毒症期间人类单细胞转录特征的动态变化
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2021-09-24 , DOI: 10.1002/jlb.5ma0721-825r
Xinru Qiu ₁ , Jiang Li ₂ , Jeff Bonenfant _{3,

4} , Lukasz Jaroszewski ₂ , Aarti Mittal ₃ , Walter Klein ₃ , Adam Godzik ₂ , Meera G Nair ₂

Affiliation

全身感染，尤其是慢性病患者，可能导致败血症：一种爆发性、不协调的免疫反应，可导致多系统器官衰竭，死亡率很高。诊断时具有相似临床表型或脓毒症生物标志物表达的患者可能有不同的结果，这表明脓毒症的动态变化在疾病进展中至关重要。设计了一项针对革兰氏阴性菌脓毒症患者的受试者内研究，该患者具有存活和死亡结局，并对在脓毒症诊断和 6 小时之间的关键时期收集的外周血单核细胞 (PBMC) 进行了单细胞转录组学分析。该研究中的单细胞观察结果与公共数据集的趋势一致，但也确定了在数小时内发生变化的单个细胞亚群的动态效应。结果表明，血小板和红细胞前体反应是致死性败血症的驱动因素，其转录特征与严重的 COVID-19 疾病相同。还表明，缺氧应激是单核细胞和红细胞前体免疫和代谢功能障碍的驱动因素。最后，数据支持 CD52 作为脓毒症的预后生物标志物和治疗靶点，因为它在淋巴细胞中的表达动态增加，并与改善的脓毒症结果相关。总之，这项研究描述了第一个单细胞研究，该研究分析了免疫细胞群的短期时间变化及其在存活或致命败血症中的特征。

"点击查看英文标题和摘要"

Dynamic changes in human single-cell transcriptional signatures during fatal sepsis

Systemic infections, especially in patients with chronic diseases, may result in sepsis: an explosive, uncoordinated immune response that can lead to multisystem organ failure with a high mortality rate. Patients with similar clinical phenotypes or sepsis biomarker expression upon diagnosis may have different outcomes, suggesting that the dynamics of sepsis is critical in disease progression. A within-subject study of patients with Gram-negative bacterial sepsis with surviving and fatal outcomes was designed and single-cell transcriptomic analyses of peripheral blood mononuclear cells (PBMC) collected during the critical period between sepsis diagnosis and 6 h were performed. The single-cell observations in the study are consistent with trends from public datasets but also identify dynamic effects in individual cell subsets that change within hours. It is shown that platelet and erythroid precursor responses are drivers of fatal sepsis, with transcriptional signatures that are shared with severe COVID-19 disease. It is also shown that hypoxic stress is a driving factor in immune and metabolic dysfunction of monocytes and erythroid precursors. Last, the data support CD52 as a prognostic biomarker and therapeutic target for sepsis as its expression dynamically increases in lymphocytes and correlates with improved sepsis outcomes. In conclusion, this study describes the first single-cell study that analyzed short-term temporal changes in the immune cell populations and their characteristics in surviving or fatal sepsis. Tracking temporal expression changes in specific cell types could lead to more accurate predictions of sepsis outcomes and identify molecular biomarkers and pathways that could be therapeutically controlled to improve the sepsis trajectory toward better outcomes.

更新日期：2021-11-30

点击分享查看原文

点击收藏

公开下载

阅读更多本刊新发论文本刊介绍/投稿指南