Single-cell transcriptomic profiling of peripheral blood mononuclear cells reveals monocyte heterogeneity in patients with Moyamoya disease

Abstract Objective Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive stenosis or occlusion of the internal carotid artery, with an abnormal vascular network forming as compensation. The etiology of MMD remains largely unknown, though genetic and immune factors have been implicated. This study aimed to investigate the landscape of peripheral immune cells in MMD patients using single-cell RNA sequencing (scRNA-seq) to identify potential biomarkers and mechanisms involved in the disease. Methods Peripheral blood mononuclear cells (PBMCs) were collected from six MMD patients and three controls. scRNA-seq was performed to analyze the transcriptomic profiles of various immune cell populations. Differential gene expression, functional enrichment, and cell interaction analyses were conducted to identify significant alterations in immune cell subpopulations. Additionally, trajectory analysis was used to explore the differentiation pathways of monocytes in MMD. Results The study identified significant transcriptional alterations in peripheral immune cells, particularly in monocytes and natural killer (NK) cells. Notably, intermediate monocytes (Mono_CD14_CD16) were increased in MMD patients compared to controls. Functional enrichment analysis revealed upregulation of genes related to immune cell activation and signal transduction in MMD. Two previously uncharacterized genes, RETN and TGFBR2, were identified as potential biomarkers. Trajectory analysis suggested that classical monocytes may differentiate into intermediate monocytes in MMD. Cell interaction analysis highlighted the role of Mono_CD14_CD16 cells in mediating immune responses through interactions involving RETN and TGF-β signaling pathways. Conclusions This study provides a comprehensive analysis of peripheral immune cell alterations in MMD, highlighting the involvement of monocyte subpopulations and specific signaling pathways in disease pathogenesis. The findings offer new insights into the immune dysregulation in MMD and suggest potential targets for diagnosis and treatment.