Perivascular adipose tissue (PVAT) is thought to play a role in vascular homeostasis and in the pathogenesis of diseases of large vessels, including abdominal aortic aneurysm (AAA). We tested the hypothesis that locally restricted transcriptional profiles characterize PVAT surrounding AAA. Using a genome-wide approach, we investigated the PVAT transcriptome of AAA in 30 patients with either large (55 mm) or small (<55 mm) aneurysm diameter. We performed a data adjustment step using the DaMiRseq R/Bioconductor package, to remove the effect of confounders as produced by high-throughput gene expression techniques. We compared PVAT of AAA with PVAT of not-dilated abdominal aorta of each patient to limit the effect of inter-individual variability, using the limma R/Bioconductor package. We found highly consistent differences in PVAT gene expression clearly distinguishing PVAT of AAA from PVAT of not-dilated aorta, which increased in number and magnitude with increasing AAA diameter. These changes did not systemically affect other abdominal adipose depots (omental or subcutaneous fat). We dissected putative mechanisms associated with PVAT involvement in AAA through a functional enrichment network analysis: both innate and adaptive immune-response genes along with genes related to cell-death pathways, metabolic processes of collagen, sphingolipids, aminoglycans and extracellular matrix degradation were strongly overrepresented in PVAT of AAA compared with PVAT of not-dilated aorta. Our results provide support to a possible role of PVAT in AAA pathogenesis and suggest that AAA is an immunologic disease with an underlying autoimmune component. These disease-specific expression signatures could help identifying pharmacological targets for preventing AAA progression.
Genome-Wide Expression Profiling Unveils Autoimmune Response Signatures in the Perivascular Adipose Tissue of Abdominal Aortic Aneurysm.
Sex, Age, Specimen part, Subject
View SamplesWe obtained global measurements of decay and translation rates for mammalian mRNAs with alternative 3'' untranslated regions (3'' UTRs). Overall design: 1 3P-Seq sample from 3T3 cells and 1 3P-Seq sample from mouse ES cells; 2 2P-Seq steady state and 4 2P-Seq with actinomycin D; 6 polysome fraction 2P-Seq
3' UTR-isoform choice has limited influence on the stability and translational efficiency of most mRNAs in mouse fibroblasts.
Specimen part, Treatment, Subject
View SamplesWe profiled genome-wide gene expression of 170 individual mid-gestation (embryonic day 11.5) whole mouse embryos derived from a 2-generation interspecies mouse cross and asked to what extent genetic variation drives four important parameters of regulatory architecture: allele-specific expression (ASE), imprinting, trans-regulatory effects, and maternal effect. The inbred strain C57BL/6J and wild-derived inbred strain CAST/EiJ were used in reciprocal crosses to generate F1 embryos. F1 progeny were backcrossed to C57BL/6J in reciprocal crosses to generate 154 N2 embryos. We employed a backcross design, in which N2 offspring have genotypically distinct parents, to enable comparison of gene expression for offspring from each side of the reciprocal cross. Our findings demonstrate that genetic variation contributes to widespread gene expression differences during mammalian embryogenesis. Overall design: Transcriptome analysis of E11.5 mouse embryos: 16 F1 embryos from reciprocally crossed C57BL/6J and CastEi/J parents; and 154 N2 embryos from reciprocal backcross of F1s to the C57BL/6J parent.
Constraint and divergence of global gene expression in the mammalian embryo.
No sample metadata fields
View SamplesRNA was obtained from histologically normal bronchial epithelium of never, former, and current smokers undergoing fiberoptic bronchoscopy.
Reversible and permanent effects of tobacco smoke exposure on airway epithelial gene expression.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.
Cell line
View SamplesTo characterize the sequence of events associated with RasV12 immortalization of Drosophila embryonic cells, we generated transcriptional time series during cell line establishment, from primary cultures until passage (P) 19. Overall design: We generated three transcriptional time series from three cell lines (R1, R4 and R5) by sampling the cultures at successive stages, early (P2-4), intermediate (P4-11), and late (P16-19), characterized by different passage times. Time points for the R1 time-series were: P2, P3, P4, P5, P7, P8, P10, P11, P16, P17 and P19; for the R4 time-series: P2, P3, P4, P5, P6, P7, P9, P11, P12, P16, P17 and P19; and for the R5 time-series: P2, P3, P4, P6, P7, P8, P16, P17 and P19
Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.
Cell line, Subject
View SamplesTo characterize the sequence of events associated with RasV12 immortalization of Drosophila embryonic cells, we generated transcriptional time series during cell line establishment, from primary cultures until passage (P) 19.
Discovery of progenitor cell signatures by time-series synexpression analysis during Drosophila embryonic cell immortalization.
Cell line
View SamplesTo identify genes expressed during initiation of lung organogenesis, we generated transcriptional profiles of the prospective lung region of the mouse foregut (mid-foregut) microdissected from embryos at three developmental stages between embryonic day 8.5 (E8.5) and E9.5. This period spans from lung specification of foregut cells to the emergence of the primary lung buds. We identified a number of known and novel genes that are temporally regulated as the lung bud forms. Genes that regulate transcription, including DNA binding factors, co-factors, and chromatin remodeling genes, are the main functional groups that change during lung bud formation. Members of key developmental transcription and growth factor families, not previously described to participate in lung organogenesis, are expressed in the mid-foregut during lung bud induction. These studies also show early expression in the mid-foregut of genes that participate in later stages of lung development. This characterization of the mid-foregut transcriptome provides new insights into molecular events leading to lung organogenesis.
Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction.
No sample metadata fields
View SamplesA number of studies have shown that cigarette smoking produces a field defect, such that genetic mutations induced by smoking occur throughout the lung and its intra and extra-pulmonary airways. Based on this concept, we have begun this study, which has as its goal the definition of the normal airway transcriptome, an analysis of how that transcriptome is affected by cigarette smoke, and to explore the reversibility of altered gene expression when smoking has been discontinued. We have obtained brushings from intra-pulmonary airways (the right upper lobe carina) and scrapings from the buccal mucosa, from normal smoking and non-smoking volunteers (including 34 Current Smokers, 23 Never Smokers and 18 Former Smokers). RNA was isolated from these samples and gene expression profiles from intra-pulmonary airway epithelial cells were analyzed using Affymetrix U133A human gene expression arrays. All microarray data from the experiments described above have been stored, preprocessed and analyzed in a relational MySQL database that is accessible through our website at http://pulm.bumc.bu.edu/aged
Effects of cigarette smoke on the human airway epithelial cell transcriptome.
Sex, Age, Specimen part, Race, Subject
View SamplesWe compared different mouse cancer cell lines to identify their unique cell signatures.
Tumor-derived osteopontin isoforms cooperate with TRP53 and CCL2 to promote lung metastasis.
Cell line
View Samples