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SRP140515
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
- 36 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We integrated three transplant rejection microarray studies examining gene expression in samples from pediatric renal, adult renal, and adult heart transplants. We performed one study ourselves and retrieved two others from the NCBI Gene Expression Omnibus (GEO)(GSE4470 and GSE1563). We identified 45 genes that were upregulated in common in acute rejection. Half were involved in one immune-related pathway. Among ten proteins we tested by serum ELISA, three successfully distinguished acute rejection from stable transplants. These were CXCL9, PECAM1, and CD44, with areas under the receiver operating characteristic curves of 0.844, 0.802, and 0.738, respectively. Immunohistochemistry showed that the PECAM1 protein was increased in acute rejection in renal, liver and heart transplants versus normal tissues. Our results show that integrating publicly-available gene expression data sets is a fast, powerful, and cost-effective way to identify serum-detectable diagnostic biomarkers.
Publication Title
Integrative urinary peptidomics in renal transplantation identifies biomarkers for acute rejection.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background
Publication Title
A systems biology approach reveals common metastatic pathways in osteosarcoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and observed a progressive enrichment in quiescent cells in these with time of culture; these cells were sorted, as their cycling counterparts, and their transcriptomes were compared. We used microarrays to detail the differential global gene expression profile between quiescent and cycling cells isolated from MALC.
Publication Title
Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Follicular Lymphomas are blood tumors growing as spheres in patients. Before this study, there was no experimental model mimicking the 3D organization of these in vivo tumors. We develop such a model, called MALC, and performed a pan-genomic comparative analysis between MALC and classical suspension cultures. We used microarrays to detail the global gene expression profile induced by aggregated growth of lymphoma cells.
Publication Title
Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Summary: Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function
Publication Title
Melanoma spheroids grown under neural crest cell conditions are highly plastic migratory/invasive tumor cells endowed with immunomodulator function.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Exhaustion markers are expressed by T lymphocytes in Follicular Lymphoma (FL). Through these, TIM-3 has been recently identified as a poor pronostic factor when expressed by FL CD4+ T cells.
Publication Title
Impaired functional responses in follicular lymphoma CD8<sup>+</sup>TIM-3<sup>+</sup> T lymphocytes following TCR engagement.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study, we examined the differential RNA profile of LY500307-treated B16 cells compared with control-treated B16 cells Overall design: We used RNA sequencing to compare the differential RNAs of LY500307-treated B16 cells compared with control-treated B16 cells
Publication Title
Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Aberrant activation of the human sex-determining gene in early embryonic development results in postnatal growth retardation and lethality in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples