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Single-nuclei sequencing of late gestation rhesus macaques exposed to chorioamnionitis

ABSTRACT: Single-nuclei sequencing of late gestation rhesus macaques exposed to chorioamnionitis

PROVIDER: PRJNA843047 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19430710_1.fastq.gz	Fastqsanger.gz
	SRR19430710_2.fastq.gz	Fastqsanger.gz
	SRR19430711_1.fastq.gz	Fastqsanger.gz
	SRR19430711_2.fastq.gz	Fastqsanger.gz
	SRR19430712_1.fastq.gz	Fastqsanger.gz

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Single-nuclei sequencing of late gestation rhesus macaques exposed to chorioamnionitis

Project description:We used single-nuclei sequencign to determine the effect of chorioamnionitis to the developing cerebellum using a rhesus macaque model of chorioamnionitis induced by intra-amniotic LPS.

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Impact of chorioamnionitis exposure on neonatal monocyte H3K4me3 patterning

Project description:We sought to determine the impact of chorioamnionitis exposure on the neonatal monocyte H3K4me3 histone modification landscape over the course of fetal and neonatal immune system development using ChIP-seq. H3K4me3 ChIP-seq was performed on umbilical cord blood purified CD14+ monocytes from healthy and chorioamnionitis-exposed extremely preterm neonates (under 30 weeks gestation), late preterm neonates (30-36 weeks gestation), and term neonates (37+ weeks gestation).

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Project description:Purpose: Our goal was to evaluate the pathways through which chorioamnionitis induces fetal lung maturation and how it interacts with a low-dose treatment with antenatal corticosteroids to further enhance fetal lung maturation. Methods: We treated pregnant rhesus macaque at 132 days (80% gestation) with intre-amniotic bacterla lipopolissacharide to model chorioamnionitis or a low-dose antenatal corticosteroids treatment with betamethasone-acetate (Beta-Ac 0.125mg/kg) or both treatments. Fetuses were delivered by c-section after 5 days and RNA-sequencing of whole lung tissue was performed. Another group of fetuses exposed to LPS was delivered 16h after treatment. Preterm controls were delivered at 132 days and term controls were delivered at 155 days and received no intervention. Results: Treatment with Beta-Ac in the setting of chorioamnionitis improves lung compliance and increases surfactant production relative to either treatment alone. RNA sequencing shows that these changes are mediated by suppression of proliferation and induction of mesenchymal cellular death. The combined exposure results in a mature-like transcriptomic profile with inhibition of extracellular matrix development by suppression of collagen genes and regulators of lung development. ACS and inflammation also suppressed signature genes associated with proliferative mesenchymal progenitors similar to the term lung. Conclusion: Treatment with ACS in the setting of inflammation may result in early respiratory advantage to preterm infants, but this advantage may come at a cost of abnormal extracellular matrix development which may be associated with increased risk of chronic lung disease.

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The Amniotic Fluid Proteome Changes Across Gestation in Humans and Rhesus Macaques

Project description:Amniotic fluid is a complex biological medium that offers mechanical protection and nutrition to the fetus, and also plays a key role in normal fetal growth, organogenesis, and potentially fetal programming. Amniotic fluid is also critically involved in longitudinally shaping the in utero milieu during pregnancy. Yet, the molecular mechanism of action by which amniotic fluid regulates fetal development is ill-defined partly due to an incomplete understanding of the evolving composition of the amniotic fluid proteome. Prior research consisting of cross-sectional studies suggests that the amniotic fluid proteome changes as pregnancy advances, yet longitudinal alterations have not been confirmed because repeated sampling is prohibitive in humans. We therefore performed serial amniocenteses at early, mid, and late gestational time-points within the same pregnancies in a rhesus macaque model. Longitudinally-collected rhesus amniotic fluid samples were paired with gestational-age matched cross-sectional human samples. Utilizing LC-MS/MS isobaric labeling quantitative proteomics, we demonstrate considerable cross-species similarity between the amniotic fluid proteomes and large scale gestational-age associated changes in protein content throughout pregnancy. This is the first study to establish a reference proteomic profile across gestation. This non-human primate model holds promise as a translational platform for amniotic fluid studies and to identify adversely affected pregnancies.

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