CD133+ progenitor cells promote pulmonary hypertension through CXCR4 signaling

Authors

Wang, Z., YI, D., Zhang, X., Dai, J., Zhang, X., Zhao, Y., Dai, Z.

Abstract

Background: Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and smooth muscle cell accumulation, but the progenitor-like cells that contribute to this process remain incompletely defined. Methods: We combined analyses of human pulmonary arterial hypertension lungs and experimental PH models with bulk and single-cell RNA sequencing, lineage tracing, inducible ablation of CD133+ cells, and conditional deletion of Cxcr4 in CD133+ cells. Results: CD133 expression was markedly increased in human and experimental PH lungs. Transcriptomic analyses identified inflammatory, metabolic, chemokine-associated, and smooth muscle cell-like programs in CD133+ cells from PH lungs. Lineage tracing showed that CD133+ cells contributed to endothelial and smooth muscle cell compartments during experimental PH. Genetic ablation of CD133+ cells attenuated hypoxia-induced PH and pulmonary vascular remodeling, whereas Cxcr4 deletion in CD133+ cells reduced PH severity. Conclusions: CD133+ progenitor cells are functional contributors to pulmonary vascular remodeling, and CXCR4 signaling mediates their pathogenic activity. Targeting pathogenic CD133+ cell states or CXCL12/CXCR4 signaling may provide a strategy to limit vascular remodeling in PH.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 04 Aug 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.