Single-cell transcriptomic, transcriptomic, and metabolomic characterization of human atherosclerosis

Area of Science:

• Cardiovascular Research
• Genomics and Bioinformatics
• Cellular Biology

Background:

• Atherosclerosis is a primary driver of cardiovascular and cerebrovascular diseases.
• Understanding intercellular connections and key genes in plaque formation is crucial.
• Current knowledge requires deeper insights into the molecular mechanisms of atherosclerosis.

Purpose of the Study:

• To comprehensively analyze genetic and molecular data for atherosclerosis.
• To identify key genes, signaling pathways, and cellular interactions in atherosclerotic plaque development.
• To investigate the role of the AGE-RAGE signaling pathway in diabetic atherosclerosis.

Main Methods:

• Utilized comprehensive bioinformatics analysis on single-cell sequencing and bulk transcriptome/metabolomic data.
• Performed differential genetic screening and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation.
• Analyzed protein-protein interactions (PPIs), pseudo-timing, intercellular communication, and transcription factors.

Main Results:

• Identified ten distinct cell types involved in atherosclerosis.
• Characterized differentiation trajectories, interaction networks, and transcription factors for endothelial, fibroblast, macrophage, and smooth muscle cells.
• Discovered the AGE-RAGE signaling pathway as critical in diabetic atherosclerosis and linked metabolites to fibroblast involvement.

Conclusions:

• Provides key genes, signaling pathways, and cellular communication insights for atherosclerotic plaque research.
• Identifies critical transcription factors and cell types (endothelial, fibroblast, macrophage, smooth muscle) in atherosclerosis.
• Offers a foundation for improved diagnosis and treatment strategies for atherosclerosis and related conditions.