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GSE51021
Homo sapiens
25 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Lymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
Publication Title
Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The cytosolic protein Sharpin is as a component of the linear ubiquitin chain assembly complex (LUBAC), which regulates NF-B signaling in response to specific ligands. Its inactivating mutation in Cpdm (chronic proliferative dermatitis mutation) mice causes multi-organ inflammation, yet this phenotype is not transferable into wildtype mice by hematopoietic stem cell transfer. Recent evidence demonstrated that Cpdm mice additionally display low bone mass, but the cellular and molecular causes of this phenotype remained to be established. Here we have applied non-decalcified histology together with cellular and dynamic histomorphometry to perform a thorough skeletal phenotyping of Cpdm mice. We show that Cpdm mice display trabecular and cortical osteopenia, solely explained by impaired bone formation, whereas osteoclastogenesis is unaffected. We additionally found that Cpdm mice display a severe disturbance of articular cartilage integrity in the absence of joint inflammation, supporting the concept that Sharpin-deficiency affects mesenchymal cell differentiation. Consistently, Cpdm mesenchymal cells displayed reduced osteogenic capacitiy ex vivo, yet this defect was not associated with impaired NF-B signaling. A molecular comparison of wildtype and Cpdm bone marrow cell populations further revealed that Cpdm mesenchymal cells produce higher levels of Cxcl5 and lower levels of IL1ra. Collectively, our data demonstrate that skeletal defects of Cpdm mice are not caused by chronic inflammation, but that Sharpin is as a critical regulator of mesenchymal cell differentiation and gene expression. They additionally provide an alternative molecular explanation for the inflammatory phenotype of Cpdm mice and the absence of disease transfer by hematopoetic stem cell transplantation.
Publication Title
Sharpin Controls Osteogenic Differentiation of Mesenchymal Bone Marrow Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We report that IL-17A has an inhibitory effect on osteoblastogenesis. Overall design: Pre-osteoblasts were treated with vehicle or 50ng/ml IL-17A for 7 days.
Publication Title
Chronic skin inflammation leads to bone loss by IL-17-mediated inhibition of Wnt signaling in osteoblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
We use single-cell RNA-seq to determine distinct selection phenotypes of 2 rare thymic Treg cell progenitors as well as mature thymic Treg cells Overall design: A single cell suspension was generated from murine thymus then magnetically depleted for CD8/Ter119 before sorting CD25+Foxp3-, CD25-Foxp3lo and CD25+Foxp3+ cells from CD4+CD73- thymocytes on a BD Aria II. The 10x Genomic platform…
Publication Title
Thymic regulatory T cells arise via two distinct developmental programs.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Homo sapiens
- 182 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma.
Publication Title
A genomic score prognostic of outcome in trauma patients.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of this analysis was to investigate the changes in the gene expression pattern of ex vivo cultured wildtype murine osteoclasts during the course of osteoclastogenic differentiation.
Publication Title
The Lysosomal Protein Arylsulfatase B Is a Key Enzyme Involved in Skeletal Turnover.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The hormone calcitonin (CT) is primarily known for its pharmacologic action as an inhibitor of bone resorption, yet CT-deficient mice display increased bone formation. These findings raised the question about the underlying cellular and molecular mechanism of CT action. Here we show that either ubiquitous or osteoclast-specific inactivation of the murine CT receptor (CTR) causes increased bone formation. CT negatively regulates the osteoclast expression of Spns2 gene, which encodes a transporter for the signaling lipid sphingosine 1-phosphate (S1P). CTR-deficient mice show increased S1P levels, and their skeletal phenotype is normalized by deletion of the S1P receptor S1P3. Finally, pharmacologic treatment with the non-selective S1P receptor agonist FTY720 causes increased bone formation in wildtype, but not in S1P3-deficient mice. This study redefines the role of CT in skeletal biology, confirms that S1P acts as an osteoanabolic molecule in vivo, and provides evidence for a pharmacologically exploitable crosstalk between osteoclasts and osteoblasts.
Publication Title
Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 856 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global
Publication Title
A genomic storm in critically injured humans.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 587 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip.
Publication Title
Genomic responses in mouse models poorly mimic human inflammatory diseases.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 177 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury.
Publication Title
Analysis of factorial time-course microarrays with application to a clinical study of burn injury.
Sample Metadata Fields
Sex, Disease
View Samples