Identification of genes involved in trophoblast differentiation is of great interest in understanding cellular and molecular mechanisms involved in placental development and is relevant clinically to fetal development, fertility, and maternal health. To understand, on a global scale, changes in the transcriptome during the differentiation of hESCs down the trophoblast lineage, a large-scale microarray analysis was performed. This work provides an in vitro functional genomic model with which to identify genes involved in trophoblast development.
Transcriptomic signature of trophoblast differentiation in a human embryonic stem cell model.
Specimen part, Cell line
View SamplesAvian coccidiosis is a major disease of poultry caused by the intestinal protozoa Eimeria. Aviagen line A and line B birds show differential susceptibility to Eimeria infection, with line B birds exhibiting higher lesion scores and mortality. The objective of this study was to examine differential intestinal gene expression between line A and B chicks in response to a challenge with Eimeria maxima. Following challenge with 1 x 10^4 oocysts/chick, greater than 40% of line A chicks had lesion scores of 0 to 1 (on 0 to 4 scale), similar to controls. In contrast, all line B challenged chicks at this same dose had lesion scores of 2 to 4.
An antimicrobial peptide is downregulated in the small intestine of Eimeria maxima-infected chickens.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Age, Specimen part
View SamplesE-cig use is continuing to increase, particularly among youth never-smokers, and is used by some smokers to quit. The acute and chronic toxicity of e-cig use is unclear generally in the context of increasing reports of inflammatory-type pneumonia in some e-cig users. To assess lung effects of e-cigs without nicotine or flavors, we conducted a pilot study with serial bronchoscopies over 4 weeks in 30 never-smokers, randomized either to a four-week intervention with the use of e-cigs containing only 50% propylene glycol (PG) and 50% vegetable glycerine (VG) or to a no-use control group. Compliance to the e-cig intervention was assessed by participants sending daily puff counts and by urinary propylene glycol (PG). Inflammatory cell counts and cytokines were determined in bronchoalveolar lavage (BAL) fluids. Genome-wide expression, microRNA, and mRNA were determined from bronchial epithelial cells. There were no significant differences in changes of BAL inflammatory cell counts or cytokines between baseline and follow-up, comparing the control and e-cig groups. However, in the intervention but not the control group, change in urinary PG as a marker of e-cig use and inhalation, was significantly correlated with change in cell counts (cell concentrations, macrophages, and lymphocytes) and cytokines (IL-8, IL-13, and TNF-α), although the absolute magnitude of changes was small. There were no significant changes in mRNA or microRNA gene expression. Although limited by study size and duration, this is the first experimental demonstration of an impact of e-cig use on inflammation in the human lung among never-smokers.
Effects of Electronic Cigarette Constituents on the Human Lung: A Pilot Clinical Trial.
Age, Specimen part
View SamplesDespite known age-related DNA methylation (aDNAm) changes in breast tumors, little is known about aDNAm in normal breast tissues. Breast tissues from a cross-sectional study of 121 cancer-free women, were assayed for genome-wide DNA methylation. mRNA expression was assayed by microarray technology. Analysis of covariance was used to identify aDNAms. Altered methylation was correlated with expression of the corresponding gene and with DNA methyltransferase protein DNMT3A, assayed by immunohistochemistry. Publically-available TCGA data were used for replication. 1,214 aDNAms were identified; 97% with increased methylation, and all on autosomes. Sites with increased methylation were predominantly in CpG lslands and non-enhancers. aDNAms with decreased methylation were generally located in intergenic regions, non-CpG Islands, and enhancers. Of the aDNAms identified, 650 are known to be involved in cancer, including ESR1 and beta-estradiol responsive genes. Expression of DNMT3A was positively associated with age. Two aDNAms showed significant associations with DNMT3A expression; KRR1 (OR 6.57, 95% CI: 2.51-17.23) and DHRS12 (OR 6.08, 95% CI: 2.33-15.86). A subset of aDNAms co-localized within vulnerable regions for somatic mutations in breast cancer. Expression of C19orf48 was inversely and significantly correlated with its methylation level. In the TCGA dataset, 84% and 64% of the previously identified aDNAms were correlated with age in both normal-adjacent and tumor breast tissues, with differential associations by histological subtype. Given the similarity of findings in the breast tissues of healthy women and breast tumors, and the effects on gene expression, aDNAms may be one pathway for increased breast cancer risk with age.
Landscape of genome-wide age-related DNA methylation in breast tissue.
Age, Race
View SamplesAnalysis of the effects of three members of the FGF family (FGF1, FGF2 and FGF9) and bone morphogenic protein 4 (BMP4) on myelinating cultures generated from dissociated embryonic spinal cord. The results of both immediate (24 hours, T1 (24 hrs)) and long term treatments (10days, T2) give insights into the cumulative effects of sustained FGF and BMP mediated signal transduction in the pathogenesis of demyelinating diseases.
Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.
Specimen part, Treatment, Time
View SamplesFailure of remyelination in multiple sclerosis (MS) is associated with inhibition of oligodendrocyte precursor (OPC) differentiation, but the cellular and molecular mechanisms involved remain poorly understood. We now report inflammatory demyelination in MS is associated with localized expression of fibroblast growth factor 9 (FGF9) by oligodendrocytes and to a lesser extent astrocytes, and demonstrate FGF9 inhibits myelination and remyelination in vitro. This inhibitory activity is reversible and due to an off target FGF9-dependent effect on astrocytes that disrupts in the growth factor milieu required to support myelination.
Fibroblast growth factor signalling in multiple sclerosis: inhibition of myelination and induction of pro-inflammatory environment by FGF9.
Specimen part, Treatment, Time
View SamplesPeripheral whole blood transcriptome profiles of pregnant women with normal pregnancy and spontaneous preterm birth from 10-18 weeks of gestational age enrolled in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).
Transcriptome analysis of early pregnancy vitamin D status and spontaneous preterm birth.
Sex, Race
View SamplesThese experiments aim to determine global gene expression patterns in WT vs KPC isolated pancreatic fibroblasts Overall design: WT or KPC mice were isolated from pancreas and RNA-seq was performed
Stromal ETS2 Regulates Chemokine Production and Immune Cell Recruitment during Acinar-to-Ductal Metaplasia.
Specimen part, Cell line, Subject
View SamplesIndividuals with Trisomy 21 (T21) exhibit numerous hematological abnormalities, including reductions in numbers of circulating B and T lymphocytes. To elucidate molecular mechanisms underlying these phenotypes, we differentiated human isogenic disomic and trisomic pluripotent cells, and observed that trisomic cells showed defects in B cell, but not T, cell differentiation. Global gene expression of differentiated, trisomic B cells revealed reduced expression of genes encoding endothelin signaling components, namely the Endothelin Receptor B (Ednrb), and its ligand Endothelin1 (Edn1).. Depletion of Ednrb mRNA in cord blood CD34+ cells led to defective B cell differentiation, supporting an hypothesis that low expression of Ednrb in T21 contributes to intrinsic lymphoid defects. Further evidence for the role of the Ednrb pathway in B cell differentiation was obtained through CRISPR/Cas9 gene targeting in disomic and trisomic iPS cells. Knockout of Ednrb in both cell backgrounds reduced the capacity for B cell differentiation. Collectively, this work identifies downregulation of Ednrb as a causative factor for impaired B lymphocyte generation in trisomic cells, which may contribute to defects in immune function associated with T21. Furthermore, a novel role for endothelin signaling in regulation of B cell development has been identified.
Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells.
Specimen part
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