Transcriptional evaluation of the ductus arteriosus at the single cell level uncovers a requirement for vimentin for complete closure

ABSTRACT: Failure to close the ductus arteriosus immediately post-birth, patent ductus arteriosus (PDA), accounts for up to 10% of all congenital heart defects. Despite significant advances in PDA management options, including pharmacological treatment targeting the prostaglandin pathway, a proportion of patients fail to respond and must undergo surgical intervention. Thus, further refinement of the cellular and molecular mechanisms that govern vascular remodeling of this vessel is required. As anticipated, single-cell RNA sequencing on the ductus arteriosus in mouse embryos at E18.5, P0.5, and P5, revealed broad transcriptional alterations in the endothelial, smooth muscle, and fibroblast cell compartments. After close evaluation of the transcriptomic dataset, we predicted that vimentin might be required for complete closure of the vessel. Subsequent studies demonstrated that, in fact, mice with genetic deletion of vimentin fail to fully remodel the ductus arteriosus. Through single-cell RNA-sequencing and by tracking closure of the ductus arteriosus postnatally in mice, we uncovered the unexpected contribution of vimentin in driving complete closure of the ductus arteriosus potentially through regulation of the Notch signaling pathway.

ORGANISM(S): Mus musculus

PROVIDER: GSE188202 | GEO | 2022/09/26

REPOSITORIES: GEO