Exploring the role of monocyte in pulmonary embolism via single‐cell transcriptome sequencing of peripheral blood

Abstract Background Research has shown that inflammation is crucial during the occurrence and development of pulmonary embolism (PE), but few of them focused specifically on the role of monocyte. This study aims to explore the pathological response of monocyte during the course of acute PE through single‐cell RNA sequencing (scRNA‐seq), providing cellular and genetic insights for early recognition, intervention and therapeutics of PE. Methods This study recruited five patients with PE who received diagnosis and treatment at Zhongshan Hospital, Fudan University, from July 2021 to December 2021 and utilised publicly available PBMC scRNA‐seq data from four healthy volunteers in the GEO dataset GSE149689 (GSM4509015, GSM4509023, GSM4509024 and GSM4509029). Fifteen PE time‐point samples were initially collected; one PE Day 3 sample was excluded because it failed quality control, leaving 14 PE samples and four healthy donor samples, for a total of 18 peripheral blood single‐cell sequencing datasets. Results The communication signals of peripheral blood mononuclear cells dynamically changed during PE. Inflammatory regulatory genes in monocytes exhibited significant changes along the cell developmental trajectory, and monocyte dysfunction persisted throughout the onset and progression of PE. The ANNEXIN signalling pathway in CD16+ monocytes and CD16‐ monocytes may play an important role, particularly suggesting that communication between CD16+ monocytes and CD16‐ monocytes is an indicator of PE progression and may be involved in the regulation of PE exacerbation and recovery. The S100 calcium‐binding protein A8/A9 (S100A8/A9) genes and ferritin heavy chain 1/light chain (FTH1/FTL) genes may also play crucial roles in PE. Conclusion CD16+ monocytes and CD16‐ monocytes exhibited pathological responses during PE. The ANNEXIN pathway, S100A8/A9 genes and FTH1/FTL genes may also play significant roles.