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Homo sapiens
18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
OBJECTIVE: Systemic sclerosis (SSc)-related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. METHODS: Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2-3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. RESULTS: Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor (TGF)- and interferon (IFN)-regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < -0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. CONCLUSION: These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and activation, and up-regulated expression of TGF- and IFN-regulated genes
Publication Title
Association of Interferon- and transforming growth factor β-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples
GSE81294- Homo sapiens
- 20 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2), Affymetrix Multispecies miRNA-3 Array (mirna3)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
miR-155 in the progression of lung fibrosis in systemic sclerosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used.
Publication Title
miR-155 in the progression of lung fibrosis in systemic sclerosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Regeneration of skeletal muscle is dependent on the function of tissue-resident muscle stem cells (MuSC), known as satellite cells. MuSC dysfunction is central to muscle pathophysiology, including in age-associated loss of muscle regenerative capacity and congenital disorders such as Duchenne muscular dystrophy. Despite the central role of satellite cells in muscle regeneration, the signals controlling the balance between muscle stem cell quiescence, proliferation, and differentiation remain incompletely understood. Knowledge of the signals that maintain a quiescent state is particularly lacking, yet such cues are crucial to maintaining a stem cell reservoir that can meet the needs of regeneration throughout life. Here we identify Oncostatin M (OSM), a member of the interleukin-6 family of cytokines, as a potent and essential trans-acting regulator of satellite cell quiescence. Key to this discovery is the development of a novel in vivo imaging-based screening strategy allowing identification of proteins that do not induce in vitro proliferation, but instead maintain MuSCs in a non-mitotic state, poised for rapid robust expansion upon transplantation. We demonstrate that OSM induces reversible exit from the cell cycle and induction of a global transcriptional program significantly enriched within a newly established satellite cell quiescence signature. Genetic ablation of the OSM receptor in mice demonstrates that signaling via OSM/R is essential for maintenance of satellite cell quiescence, and for proper skeletal muscle regeneration in vivo. Given that aberrant activation and exhaustion of stem cells is seen in a variety of disorders, OSM constitutes an attractive therapeutic target in muscle disease states.
Publication Title
Induction of muscle stem cell quiescence by the secreted niche factor Oncostatin M.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 44 Downloadable Samples
Description
The incidence of pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but host susceptibility factors are not fully understood. We infected air-liquid interface (ALI) primary respiratory epithelial cell cultures with Mycobacterium avium complex (MAC) or Mycobacterium abscessus (MAB) and performed transcriptome sequencing (RNA-Seq) to identify relevant gene expression differences. We used cells from 4 different donors in order to try to obtain generalizable data. The differentiated respiratory epithelial cells in ALI were infected with MAC or MAB at MOI of 100:1 or 1000:1, and RNA-seq was performed at 1 and 3 days after infection. We found downregulation of ciliary genes, including several identified with polymorphisms in previous PNTM cohorts. The cytokine IL-32, the superpathway of cholesterol biosynthesis and downstream targets within the IL-17 signaling pathway were all elevated. The integrin signaling pathway was more upregulated by MAB than MAC infection. Working with primary respiratory epithelial cells infected with nontuberculous mycobacteria at ALI, we identified ciliary function, cholesterol biosynthesis, chemokine production and the IL-17 pathway as major targets of host responses to infection. Some of these pathways may be amenable to therapeutic manipulation. Overall design: 44 strand-specific RNA libraries for high-throughput sequencing were prepared (samples from 4 different donors, 57F, 75M, 69F, and 42F, for each condition) using the TruSeq Stranded mRNA Sample Preparation Kit with 750ng of total RNA according to manufacturer's instructions.
Publication Title
Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Breast cancer patients present lower 1,25(OH)2D3 or 25(OH)D3 serum levels than unaffected women. Although 1,25(OH)2D3 pharmacological concentrations of 1,25(OH)2D3 may exert antiproliferative effects in breast cancer cell lines, much uncertainty remains about the effects of calcitriol supplementation in tumor specimens in vivo. We have evaluated tumor dimension (ultrassonography), proliferative index (Ki67 expression), 25(OH)D3 serum concentration and gene expression profile, before and after a short term calcitriol supplementation (dose to prevent osteoporosis) to post-menopausal patients. Results: Thirty three patients with operable disease had tumor samples evaluated. Most of them (87.5%) presented 25(OH)D3 insufficiency (<30 ng/mL). Median period of calcitriol supplementation was 30 days. Although tumor dimension did not vary, Ki67 immunoexpression decreased after supplementation. Transcriptional analysis of 15 matched pre/post-supplementation samples using U133 Plus 2.0 GeneChip (Affymetrix) revealed 18 genes over-expressed in post-supplementation tumors. As a technical validation procedure, expression of four genes was also determined by RT-qPCR and a direct correlation was observed between both methods (microarray vs PCR). To further explore the effects of near physiological concentrations of calcitriol on breast cancer samples, an ex vivo model of fresh tumor slices was utilized. Tumor samples from another 12 post-menopausal patients were sliced and treated in vitro with slightly high concentrations of calcitriol (0.5nM), that can be attained in vivo, for 24 hours In this model, expression of PBEF1, EGR1, ATF3, FOS and RGS1 was not induced after a short exposure to calcitriol. Conclusions: In our work, most post-menopausal breast cancer patients presented at least 25(OH)D3 insufficiency. In these patients, a short period of calcitriol supplementation may prevent tumor growth and reduce Ki67 expression, probably associated with discrete transcriptional changes. This observation deserves further investigation to better clarify calcitriol effects in tumor behavior under physiological conditions.
Publication Title
Calcitriol supplementation effects on Ki67 expression and transcriptional profile of breast cancer specimens from post-menopausal patients.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 112 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Neutrophil lysis after phagocytosis is a process potentially important in the pathogenesis of community-associated methicillin-resistant S. aureus (CA-MRSA) infection. The mechanism for this process is not currently known. Therefore, to better understand CA-MRSA virulence we used human oligonucleotide microarrays to investigate the mechanism underlying enhanced PMN lysis that occurs after phagocytosis of CA-MRSA.
Publication Title
Rapid neutrophil destruction following phagocytosis of Staphylococcus aureus.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Identifying novel candidate biomarker gene differentially expressed in the peripheral blood cells of patients with early stage acute myocardial infarction using microarray as a high throughput screening technology.
Publication Title
Novel genes detected by transcriptional profiling from whole-blood cells in patients with early onset of acute coronary syndrome.
Sample Metadata Fields
Specimen part, Disease, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Stem cell differentiation is known to involve changes in RNA expression, but little is known about translational control during differentiation. We comprehensively profiled gene expression during differentiation of embryonic stem cells (ESCs) into embyroid bodies (EBs) by integrating conventional transcriptome analysis with global assessment of ribosome loading. Differentiation was accompanied by an anabolic switch, characterized by global increases in transcript abundance, polysome content, protein synthesis rates and protein content. Furthermore, 78% of expressed transcripts showed increased ribosome loading, thereby enhancing translational efficiency. Elevated protein synthesis was accompanied by enhanced phosphorylation of eIF-4E binding protein, suggesting regulation by the mTOR pathway.
Publication Title
A hierarchical network controls protein translation during murine embryonic stem cell self-renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Goal of the experiment: Analysis of gene expression changes in the cortex, striatum, hippocampus, hypothalamus, Drd2-MSNs and Drd1-MSNs of mice with a postnatal, neuron-specific ablation of GLP or G9a as compared to control mice.
Publication Title
Control of cognition and adaptive behavior by the GLP/G9a epigenetic suppressor complex.
Sample Metadata Fields
Specimen part
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