Abstract： Objective:This study aims to explore the characteristics of differentially expressed genes (DEGs) and intercellular communication in the tissues of patients with pulmonary arterial hypertension (PAH) by analyzing high-throughput gene expression and single-cell RNA sequencing data. The ultimate goal is to unveil the molecular mechanisms and cellular behavior heterogeneity associated with PAH.Methods:Gene expression datasets GSE244830 and single-cell expression dataset GSE228644 were downloaded from the GEO databaseof NCBI. Differential gene analysis was carried out using the limma package, and functional enrichment analysis using the clusterProfiler package. Single-cell data were analyzed for cell clustering and pseudotime trajectories using the Seurat and monocle packages, respectively. Intercellular communication was assessed with the CellChat package. All analyses were performed in the R programming environment.Results:From the GSE244830 dataset, 81 significant DEGs were identified, with 70 upregulated and 11 downregulated in the PAH group. Further PPI analysis identified 8 hub genes fromthe 81 DEGs. Enrichment results showed that the DEGs are primarily involved in biological processes such as proliferation of epithelial and endothelial cells and participate in the regulation of the glycoprotein-mediated AGE-RAGE signaling pathway. Single-cell type annotation revealed that 16, 430 cells were classified into 9 cell types, including monocytes, CD8+ T cells, adipocytes, NK cells, endothelial cells, epithelial cells, fibroblasts, hematopoietic stem cells, and macrophages. The single-cell pseudotime analysis indicated activation of multiple genes during the progression of PAH, involving cellular adhesion, cytoskeletal stability, and cell-mediated immune response. The cell communication results highlighted that fibroblasts and adipocytes are the main communicative cells in the development of PAH, particularly in the COLLAGEN signaling pathway.Conclusion:This study reveals tissue-specific gene expression patterns in PAH patients at the cellular level, providing new insights into the pathophysiological mechanisms of PAH, and holds potential clinical significance for developing targeted treatment strategies.