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

Area of Science:

• Vascular Biology
• Immunology
• Genomics

Background:

• Moyamoya disease (MMD) pathogenesis and arterial pathology are not fully understood.
• Comprehensive cellular and molecular characterization of MMD-affected arteries is needed.

Purpose of the Study:

• To map the cellular composition and molecular landscape of pathological arteries in Moyamoya disease.
• To elucidate the roles of immune and vascular cells in MMD pathogenesis.

Main Methods:

• Single-cell RNA sequencing of superficial temporal artery samples from MMD patients and controls.
• Differential gene expression, pathway enrichment, and cell-cell communication analyses.
• In vitro validation of cell interactions and functional effects.

Main Results:

• Identified 8 major cell types, with an increased proportion of smooth muscle cells (SMCs) in MMD arteries.
• Detected heightened immune activity, particularly in natural killer T cells.
• Demonstrated that macrophage migration inhibitory factor pathway mediates immune cell, SMC, and endothelial cell (EC) interactions, promoting EC proliferation and angiogenesis.

Conclusions:

• Provides a single-cell transcriptomic map of MMD superficial temporal arteries.
• Highlights critical roles of immune cells, especially natural killer T cells, in promoting SMC and EC proliferation, migration, and angiogenesis.
• Suggests potential therapeutic targets for Moyamoya disease by elucidating immune-vascular cell crosstalk.