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GSE2873
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These experiments are designed to discover genes that are expressed selectively by synaptic nuclei in skeletal muscle with the particular goal of identifying genes that regulate motor axon growth and differentiation.
Publication Title
CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Ischemia reperfusion (I/R) injury is an unavoidable event occurring during heart transplantation, leading to graft failures and lower long-term survival rate of the recipient. IR causes apoptosis / death of cardiomyocytes, resulting from up-regulation of apoptotic genes and down-regulation of anti-apoptotic genes.
Publication Title
MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation.
Sample Metadata Fields
Specimen part, Time
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
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