Enhanced prenatal fatty streak formation in human fetuses has been associated with maternal hypercholesterolemia. However, the possible roles of maternal genetic background and in utero environment on development of atherosclerosis in adult life have not been unraveled. We generated genetically identical heterozygous apoE-deficient mice offspring with a different maternal background to study the intrauterine effect of maternal genotype and associated hypercholesterolemia on the developing vascular system. As read out for increased atherosclerosis development in adult life, a constrictive collar was placed around the carotid artery to induce lesion formation. A significant increase in endothelial cell activation and damage was detected in the carotid arteries of heterozygous apoE-deficient fetuses with apoE-deficient mothers compared with offspring from wild type mothers, but no fatty streak formation was observed. Postnatally, all carotid arteries revealed normal morphology. In adult offspring with maternal apoE-deficiency, the constrictive collar resulted in severe lesion (9/10) development compared with no to only minor lesions (2/10) in offspring of wild type mothers. Microarray analysis showed no effect of maternal apoE-deficiency on gene expression in adult offspring. We conclude that maternal apoE-deficiency not only affects fetal arteries, but also increases the susceptibility for development of collar-induced atherosclerosis in adult life.
Intrauterine exposure to maternal atherosclerotic risk factors increases the susceptibility to atherosclerosis in adult life.
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View SamplesCircadian profiling of total RNA collected from wildtype and NPY KO murine liver. Liver RNA collected every 4 hours in a 12hr light:12hr dark cycle.
Neural clocks and Neuropeptide F/Y regulate circadian gene expression in a peripheral metabolic tissue.
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View SamplesRNA-seq analysis of zebrafish foxc1a mutant Overall design: For RNA-seq, mRNA was extracted from 38-40 hpf old embryos. We isolated wild type and foxc1a mutant samples by dissecting the entire first 6 anterior somitic segments (AS) through which the fin nerves migrate, and the adjacent posterior segments (PS; segments 7 through ~12) devoid of fin innervating nerves. Heads and yolks were excluded from all samples. Tissues were stored in RNAlater solution (Life Technologies) for up to 2 days at 4 degree before RNA was extracted using the RNAeasy kit (Qiagen) according to the manufacture’s protocol. RNA was tested for integrity using a Bioanalyzer (Agilent technologies). RNA samples showing RIN value of 8 or higher were used for generating cDNA libraries as described in the TruSeq® Stranded mRNA sample preparation guide. At the final stage, 15 cycles of PCR amplifications was performed. Barcoded libraries representing duplicates of AS and PS samples of wild type and mutants were validated using Bionalyzer (Agilent Technology) and finally sequenced in Illumina HiSeq 2500 yielding paired end reads of 100bp. The RNA-seq Unified Mapper (RUM) (Grant et al., 2011) was used to align the reads to the Zv9/danRer7 reference genome and to assign each read uniquely to a transcript. We investigated transcripts that showed the highest fold changes of expression between the different groups. For Gene Ontology annotations, genes tagged by the GO term “axon guidance” were obtained from the gene ontology database (http://www.geneontology.org/). Next we filtered this list for the “Danio rerio” taxon (resulting in 116 unique genes) and used them to annotate our RNA-seq results.
Zebrafish foxc1a drives appendage-specific neural circuit development.
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View SamplesThis is to determine in vivo kidney tissue gene expression regulated by acetate feeding in drinking water into mice for 6 weeks.
Chronically Elevated Levels of Short-Chain Fatty Acids Induce T Cell-Mediated Ureteritis and Hydronephrosis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A circadian gene expression atlas in mammals: implications for biology and medicine.
Specimen part
View SamplesTo characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional rush hours preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.
A circadian gene expression atlas in mammals: implications for biology and medicine.
Specimen part
View SamplesDendritic cells (DC) serve a key function in host defense, linking innate detection of microbes to the activation of pathogen-specific adaptive immune responses. Whether there is cell-intrinsic recognition of HIV-1 by host innate pattern-recognition receptors and subsequent coupling to antiviral T cell responses is not yet known. DC are largely resistant to infection with HIV-1, but facilitate infection of co-cultured T-helper cells through a process of trans-enhancement. We show here that, when DC resistance to infection is circumvented, HIV-1 induces DC maturation, an antiviral type I interferon response and activation of T cells. This innate response is dependent on the interaction of newly-synthesized HIV-1 capsid (CA) with cellular cyclophilin A (CypA) and the subsequent activation of the transcription factor IRF3. Because the peptidyl-prolyl isomerase CypA also interacts with CA to promote HIV-1 infectivity, our results suggest that CA conformation has evolved under opposing selective pressures for infectivity versus furtiveness. Thus, a cell intrinsic sensor for HIV-1 exists in DC and mediates an antiviral immune response, but it is not typically engaged due to absence of DC infection. The virulence of HIV-1 may be related to evasion of this response, whose manipulation may be necessary to generate an effective HIV-1 vaccine.
A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells.
Specimen part
View SamplesLarge scale transcriptome analysis of Wistar and Sprague Dawley rat tissues.
Applications of a rat multiple tissue gene expression data set.
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View SamplesTo get more insight in cause and consequences of proteinuria, we studied glomerular gene expression patterns before and after the onset of increased urinary albumin excretion in a proteinuric rat strain.
Increased dynamin expression precedes proteinuria in glomerular disease.
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View SamplesHigh-temporal resolution profiling was performed on mouse liver to detect rhythmic transcripts
Harmonics of circadian gene transcription in mammals.
No sample metadata fields
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