Fig. 2

Comprehensive single-cell transcriptomic analysis reveals T cell heterogeneity and functional dynamics in PAH. A UMAP plot showing the clustering and annotation of T cell subsets in PAH and healthy control samples, including CD8 + Effector, CL_CD4 + CCR6 + , Activated T, CD4 + Naïve, CD8 + Naïve, and NK cells. Each cluster represents a distinct functional subset, highlighting the heterogeneity within the T cell population. B and C Bar and pie charts displaying the proportions and counts of different T cell subsets in the PAH group and healthy controls. Activated T cells and CD8 + Effector T cells show significant increases in the PAH group, while Naïve T cells decrease, indicating enhanced immune activation in PAH. D UMAP plots displaying T cell distribution across different disease states (Con, IPAH, PHHF, SSc-PH), accompanied by line charts showing the proportion of T cell subsets in each condition. Disease-specific shifts in T cell composition are observed, with notable changes in IPAH and SSc-PH. E Monocle2 and Monocle3 pseudotime trajectories of T cell subsets, showing dynamic transitions from Naïve T cells to Activated T cells and CD8 + Effector T cells. Violin plots illustrate gene expression trends along the pseudotime axis, reflecting the functional evolution of T cells in PAH. F Heatmap of differentially expressed genes across T cell subsets, with enriched pathways annotated, including leukocyte adhesion, inflammatory response, and immune activation. Key pathways suggest that T cells contribute to inflammation, tissue remodeling, and disease progression in PAH. G Heatmap of TF activity across T cell subsets, highlighting TFs with altered activity in PAH, such as NFATC1, HIF1A, BATF, STAT1, and FOXP3. These TFs regulate immune activation, metabolic adaptation, and inflammatory processes