TNF Drives Aberrant BMP Signaling to Induce Endothelial and Mesenchymal Dysregulation in a Transgenic Model of Pulmonary Hypertension

The pathobiology of pulmonary hypertension (PH) is complex and multiple cell types (endothelial, smooth muscle, fibroblast, pericyte) contribute to disease pathogenesis. However, the specific molecular crosstalk between endothelial and mesenchymal cells to promote PH is poorly characterized. We previously demonstrated that tumor necrosis factor alpha transgenic (TNF-Tg) mice have a severe PH phenotype. Pulmonary endothelial and mesenchymal cells were isolated from WT and TNF-Tg mice at 8,14, and 20 weeks of age and underwent single-cell RNA sequencing.