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GSE76262
Homo sapiens
139 Downloadable Samples
Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Asthma is a heterogeneous disease requiring understandings at molecular level that characterizes subgroups of patients with specific biomarkers to faciliate the development of targeted thearpies.
Publication Title
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED.
Sample Metadata Fields
Sex, Age
View Samples- Sus scrofa
- 8 Downloadable Samples
- Affymetrix Porcine Genome Array (porcine)
Description
Neuregulin-1 (NRG-1) is a paracrine factor critical for cardiac development. We have been examining whether the recombinant NRG-1 isoform known as glial growth factor 2 (GGF2) has therapeutic potential for heart failure. In both small and large animals after experimental myocardial infarction (MI) we have found that GGF2 treatment improves myocardial function and limits progressive myocardial remodeling. To understand potential mechanisms for this effect, we compared gene expression in swine by microarray analysis.
Publication Title
Anti-remodeling and anti-fibrotic effects of the neuregulin-1β glial growth factor 2 in a large animal model of heart failure.
Sample Metadata Fields
Specimen part, Disease, Treatment
View Samples- Homo sapiens
- 496 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Severe asthma is a collection of disease entities with varying pathophysiological characteristics (7) that result in symptoms of cough, wheeze and breathlessness, with frequent exacerbations. To address the problem of phenotypic difference and heterogeneity, the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project was set up as a public-private partnership within the framework of the Innovative Medicines Initiative (IMI), engaging academia, the pharmaceutical industry and patient groups. The goal of this investigation was to identify transcript fingerprints in whole blood that characterize patients with severe asthma and to determine whether subgroups of severe asthmatics can be identified. Furthermore, we were interested in elucidating the biological pathways that showed differences between subgroups.
Publication Title
A Severe Asthma Disease Signature from Gene Expression Profiling of Peripheral Blood from U-BIOPRED Cohorts.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 24 Downloadable Samples
NextSeq 500
Description
Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) with asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthma is unclear. Objective: To explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthma. Methods: Primary human bronchial epithelial cell (HBEC) air-liquid interface (ALI) cultures were stimulated with IL-6 and sIL-6R to establish an IL-6TS gene signature. Two separate RNA sequencing (RNA-seq) studies were performed: The “IL-6 vs T2 study” compared gene expression after stimulation with control medium, IL-6, IL-6/sIL-6R and IL-4/IL-13, while the “JAK1-inhibition study” addressed the effect of JAK1 inhibition on IL-6TS induced gene expression. The IL-6TS gene signature was used to stratify lung epithelial transcriptomic data obtained from asthmatics (n=103) in the U-BIOPRED cohorts by hierarchical clustering. Molecular phenotyping was based on the transcriptional profiling of epithelial brushings, pathway analysis and immunohistochemistry analysis of bronchial biopsies. Results: Activation of IL-6TS in HBEC ALI cultures reduced epithelial barrier function and induced a specific epithelial gene signature enriched in airway remodeling genes. The IL-6TS signature identified a subset (n=17) of IL-6TS High asthma patients with increased epithelial expression of IL-6TS inducible genes in absence of increased systemic levels of IL-6 and sIL-6R. The IL-6TS High subset had an increased exacerbation frequency (p=0.028), blood (>300/µl; p=0.0028) and sputum (>20%; p=0.007) eosinophilia, and submucosal infiltration of CD4 T cells, CD8 T cells (p<0.001) and macrophages (p=0.001). In bronchial brushings, TLR pathway genes were up-regulated while the expression of epithelial tight junction genes was reduced (all with q<0.05). Sputum sIL-6R levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, MMP3, IL-8 and IL-1ß (all with q<0.001). Conclusions: Local lung epithelial IL-6TS activation in absence of type 2 airway inflammation defines a novel subset of asthmatics and may drive airway inflammation and epithelial dysfunction in these patients. Overall design: Primary human bronchial epithelial cells grown and differentiated on air-liquid interface were stimulated basolaterally for 24h with cytokines corresponding to IL-6TS (IL-6 + sIL-6R), IL-6 alone, a Type 2 immune response (IL-4 + IL-13) or media alone as non-stimulated control. Each stimulation condition was done in triplicates. Cells were lysed, the RNA isolated and converted into libraries then used for next generation sequencing in order to identify genes that were up- or downregulated in response to the different stimulations.
Publication Title
Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Gene expression changes were assessed from the non sun-exposed skin of the lower back of 98 healthy males aged 19-86. We show that contrary to previous thought, genome wide transcriptional activity does not display an exclusively linear correlation with ageing, but rather, in human skin, undergoes a period of significant transient change between 30 and 45 years of age. The identified transient transcriptional changes suggest a period of heightened metabolic activity and cellular damage mediated primarily through the actions of TP53 (tumour protein 53) and TNF (tumour necrosis factor). We also identified a subgroup of the population characterised by increased expression of a large group of hair follicle genes that correlates strongly with a younger age of onset and increasing severity of androgenetic alopecia.
Publication Title
Transcriptome analysis of human ageing in male skin shows mid-life period of variability and central role of NF-κB.
Sample Metadata Fields
Age, Specimen part
View Samples