What type of study is this?

This is a Single-Cell RNA Sequencing study (also classified as: In Vitro Study).

September 10, 2025Open Access

Single‐Cell Transcriptome Profiling Reveals Dynamic Cell Populations and Immune Infiltration in Moyamoya Disease

SHShihao HeCapital Medical University JZJ ZhangStanford University ZZZhenyu ZhouCapital Medical University

Key Points

Increased smooth-muscle cell proportion in moyamoya disease correlates with immune activity and vascular changes.
Single-cell RNA sequencing analysis identified 8 major cell types in the superficial temporal artery, highlighting disease-related alterations.
Cell–cell communication analysis showcased the macrophage migration inhibitory factor pathway as pivotal in immune and vascular cell interactions.
Natural killer T cells were found to enhance endothelial cell proliferation, suggesting their critical role in the vascular occlusion process.

Abstract

Background The cellular composition and molecular mechanisms of the pathological arteries in Moyamoya disease (MMD) remain poorly understood. To improve our understanding of pathogenesis in MMD, we aimed to comprehensively map the cellular composition and molecular alterations within the pathological arteries of patients with MMD. Methods Superficial temporal artery samples were collected from patients with MMD (n=2) and healthy controls (n=3), yielding a total of 26 371 cells that were used for single‐cell RNA sequencing. Differentially expressed genes, pathway enrichment, and cell–cell communication analyses were performed to examine disease‐related changes. In vitro experiments were performed to validate the changes in endothelial cells (ECs) and smooth‐muscle cells (SMCs), as well as the interactions between immune cells and ECs and SMCs. Results We identified 8 major cell types in the human superficial temporal artery. We observed an increased proportion of SMCs in the superficial temporal artery of MMD. Two distinct SMC clusters, SMC1 and SMC2, were identified and exhibited different gene expression. Immune profiling revealed significant upregulation of genes in natural killer T cells, suggesting increased immune activity in MMD. Cell–cell communication analysis highlighted the role of the macrophage migration inhibitory factor pathway in promoting interactions between immune cells, SMCs, and ECs. In vitro experiments confirmed that the colocalization of CD74 with CD44 or CXCR4 in ECs promotes EC proliferation and angiogenesis. Natural killer T cells can promote cytoskeletal enlargement in ECs and SMCs, enhancing their migratory and proliferative capacities, as well as promoting angiogenesis in ECs. Conclusions This study provides a single‐cell transcriptomic map of the superficial temporal artery in MMD, revealing key immune and vascular cell populations. Immune cells, particularly natural killer T cells, play a critical role in promoting SMC and EC proliferation and migration, contributing to vascular occlusion. These findings make contributions to understanding the pathogenesis of MMD and suggest potential therapeutic targets.

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