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Gene Profiling in Mouse Fetal Ductus Arteriosus

ABSTRACT: The ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life. We used microarrays to compare ductus arteriosis (DA) and aortic gene expression at a single time point (day 19 of gestation, which is the day of expected delivery).

ORGANISM(S): Mus musculus

PROVIDER: GSE51664 | GEO | 2014/08/05

SECONDARY ACCESSION(S): PRJNA224287

REPOSITORIES: GEO

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Gene Profiling in Mouse Fetal Ductus Arteriosus

Project description:The ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life. We used microarrays to compare ductus arteriosis (DA) and aortic gene expression at a single time point (day 19 of gestation, which is the day of expected delivery). DA and corresponding aortic vascular segments from fetal mice on day 19 of gestation were collected from every pup in a litter (up to the first 10 pups). These samples were pooled and considered representative of the DA's or aortas from one pregnant female. Tissues were homogenized via 27g needle, per GentraSystems Versagene kit

2014-08-05 | E-GEOD-51664 | biostudies-arrayexpress

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Project description:Patent ductus arteriosus (PDA) is the third most common congenital heart disease and resulted from the persistence of ductal patency after birth. Ductus arteriosus closure involves functional and structural remodeling, controlled by many factors. The closure-related human plasma proteins are unknown. Here we for the first time demonstrate six key differential plasma proteins in the human PDA patients using proteomic technology and present a model to illustrate the constriction and closure of ductus arteriosus. We found that permanent closure might be regulated by the proteins related to platelet activation and coagulation cascades, complement mannan-binding-lectin, and other systemic signaling pathways. Our findings indicate that the differential proteins involved in these pathways may play key roles in the non-closure of the ductus arteriosus and may be developed as biomarkers for diagnosis. All those findings may be served as the basis of understanding the etiology and pathogenesis of PDA.

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Project description: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.

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Expression profiling in ductus arteriosus and aorta of Brown-Norway and Fischer344 rats

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Project description:Closure or patency of the ductus arteriosus is a critical event in neonatal life. We aimed to identify genes that are specifically expressed in the ductus arteriosus versus (the non-closing) aorta Gene expression profiling of laser-captured microdissected cells offers the opportunity to study gene expression profiles in cells of different embryonic origin Comparative microarray analysis of laser-capture dissected endothelial and smooth muscle cells of the rat ductus arteriosus and aorta at embryonic age E18 and E21.

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