TNF drives aberrant BMP signaling to induce endothelial and mesenchymal dysregulation in pulmonary hypertension.

ABSTRACT: The pathobiology of pulmonary hypertension (PH) is complex and multiple cell types contribute to disease pathogenesis. We sought to characterize the molecular crosstalk between endothelial and mesenchymal cells that promote PH in the tumor necrosis factor α-transgenic (TNF-Tg) model of PH. Pulmonary endothelial and mesenchymal cells were isolated from WT and TNF-Tg mice and underwent single-cell RNA sequencing. Data were analyzed using clustering, differential gene expression and pathway analysis, ligand-receptor interaction, transcription factor binding, and RNA velocity assessments. Significantly altered ligand-receptor interactions were confirmed with immunofluorescent staining. TNF-Tg mice had increases in smooth muscle cells and Col14+ fibroblasts, and reductions in general capillary

SUBMITTER: Garcia-Hernandez ML 

PROVIDER: S-EPMC12288976 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature