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).
Project description:We sought to determine the impact of chorioamnionitis exposure on term neonatal monocyte transcription. RNA-seq was performed on term healthy and chorioamnionitis-exposed umbilical cord blood purified CD14+ monocytes under unstimulated and LPS stimulated conditions.
Project description:Adult naïve CD4 T cells demonstrate differences in H3K4me3 patterning with H3K4me3 enrichment in T cell activation pathways compared to neonatal cells.
Project description:Chromatin immunoprecipitation with massively parallel DNA sequencing (ChIP-seq) was then performed to establish the H3K4me3 landscape in neonatal and adult CD14+ monocytes. As development progressed from neonate to adult, monocytes gained the activating mark H3K4me3. The decreased H3K4me3 abundance at immunologically important neonatal monocyte gene promoters correlated with reduced gene expression, providing evidence that neonatal immune cells exist in an epigenetic state that is distinctly different from adults, and that this state contributes to neonatal specific immune responses.
Project description:To identify candidate miRNAs in amniotic fluids as biomarkers for chorioamnionitis, we compared miRNA array data in amniotic fluids between pregnant women with the absence and presence of histological 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.
Project description:Preterm premature rupture of membranes (PPROM), which precedes approximately 30–40% of preterm births, is the main cause of neonatal morbidity, mortality, and long-term sequelae. In particular, almost half of all PPRPM cases are frequently complicated by subclinical acute inflammation in the placenta and fetal tissue, commonly named as acute histologic chorioamnionitis [HCA]. Increasing evidences suggest that HCA carries additional risks to both the pregnant women and their fetuses, including greater risk of imminent preterm birth, as well as sepsis, neurologic morbidity, and mortality in neonates. More accurate and early prenatal predictive markers (especially noninvasive ones) are urgently needed for identifying subclinical HCA in the context of PPROM.To identify potential biomarkers in the plasma that could predict histologic chorioamnionitis (HCA) in women with preterm premature rupture of membranes (PPROM), using shotgun and targeted proteomic analyses.
Project description:Newborns, particularly those born prematurely, are extremely vulnerable to sepsis and this has been attributed to ‘immature’ innate monocyte defences. Predominant pathogens include Escherichia. coli and Staphylococcus. epidermidis but no studies have assessed global transcriptional responses of neonatal monocytes to live sepsis-causing bacteria. Here, we aimed to identify and characterise the common and pathogen-specific, neonatal monocyte transcriptional responses to E. coli and S. epidermidis to better understand early life innate immune responses. RNA-sequencing was performed on purified cord blood monocytes from very preterm (<32 weeks gestational age, GA) and term infants (37-40 weeks GA) following standardised challenge with live S. epidermidis or E. coli.