Filters
Technology
Platform
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Targeting protein kinase C (PKC) isoforms by the small molecule inhibitor enzastaurin has shown promising pre-clinical activity in a wide range of tumor cells. In this study, we further delineated its mechanism of action in multiple myeloma (MM) cells and found a novel role of b-catenin in regulating growth and survival of tumor cells. Specifically, inhibition of PKC leads to rapid accumulation of b-catenin by preventing the phosphorylation required for its proteasomal degradation. Microarray analysis and siRNA-mediated gene silencing in MM cells revealed that accumulated b-catenin activates early ER stress signaling via eIF2a, CHOP and p21, leading to immediate growth inhibition. Furthermore, accumulated b-catenin contributes to enzastaurin-induced cell death. Both sequential knock-down of b-catenin, c-Jun, and p73, as well as overexpression of b-catenin or p73 confirmed that accumulated b-catenin triggers c-Jun-dependent induction of p73, thereby conferring MM cell apoptosis. In summary, our data reveal a novel role of b-catenin in ER stress-mediated growth inhibition, and a new pro-apoptotic mechanism triggered by b-catenin upon inhibition of PKC isoforms. Moreover, we identify p73 as a potential novel therapeutic target in MM. Based on these and previous data, enzastaurin is currently under clinical investigation in a variety of hematologic malignancies including MM.
Publication Title
Targeting PKC: a novel role for beta-catenin in ER stress and apoptotic signaling.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE36527- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs.
Publication Title
IL-2 receptor signaling is essential for the development of Klrg1+ terminally differentiated T regulatory cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used microarrays to detail the global programme of gene expression underlying CS1-regulated biological processes including increased cell adhesion and cell proliferation.
Publication Title
CS1 promotes multiple myeloma cell adhesion, clonogenic growth, and tumorigenicity via c-maf-mediated interactions with bone marrow stromal cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Multiple Myeloma (MM) remains incurable despite novel therapies, suggesting the need for further identification of factors mediating tumorigenesis and drug resistance. We performed microarray analysis to identify the molecular mechanisms whereby pDCs confer growth and drug resistance in MM cells.
Publication Title
Functional interaction of plasmacytoid dendritic cells with multiple myeloma cells: a therapeutic target.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [HuEx10stv2_Hs_ENST_14.1.0 (huex10st)
Description
Cultures of primary human airway epithelial cells (HAE cells) were exposed to an MDCK equivalent MOI of 0.01 of several swine- and human-origin influenza viruses and RNA was extracted at the 12, 16, and 24 hours post infection.
Publication Title
25-Hydroxycholesterol acts as an amplifier of inflammatory signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to identify markers predicting responder status in tocilizumab treatment in rheumatoid arthritis in 13 patients at week 0 and week 4 of treatment.
Publication Title
Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Dyskeratosis congenita is a bone marrow failure syndrome characterized by the presence of short telomeres at presentation. The X-linked form is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for in the assembly and stability of telomerase and is also involved in ribosomal RNA (rRNA) processing where it converts specific uridines to pseudouridine. DC is thought to result from failure to maintain tissues, like blood, that are renewed by stem cell activity, suggesting induced pluripotent stem (iPS) cells from X-linked DC patients may provide information about the mechanisms involved. Here we show that in iPS cells with DKC1 mutations Q31E, A353V and L37 telomere maintenance is compromised with short telomere lengths and decreased telomerase activity. The degree to which telomere lengths are affected by expression of telomerase during reprograming, or with ectopic expression of wild type dyskerin varies, with recurrent mutation A353V showing the most severe effect on telomere maintenance. A353V cells but not Q31E or L37 cells, are refractory to correction by incorporation of a single copy of a wild type DKC1 cDNA into the AAVS1 safe harbor locus. None of the mutant cells show decreased pseudouridine levels in rRNA or defective rRNA processing. Finally transcriptome analysis of the iPS cells shows that WNT signaling is significantly decreased in all mutant cells, raising the possibility that defective WNT signaling may contribute to disease pathogenesis.
Publication Title
Impaired Telomere Maintenance and Decreased Canonical WNT Signaling but Normal Ribosome Biogenesis in Induced Pluripotent Stem Cells from X-Linked Dyskeratosis Congenita Patients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 77 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We used microarrays to identify markers predicting responder status in infliximab treatment in 19 rheumatoid arthritis and 20 Crohn's disease patients at week 0 and week 2 of treatment.
Publication Title
Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is considered a chronic inflammatory disease characterized by progressive airflow limitation and also has significant extrapulmonary (systemic) effects that lead to comorbid conditions. Very little is known about the pathomechanism of the disease.
Publication Title
Chronic obstructive pulmonary disease-specific gene expression signatures of alveolar macrophages as well as peripheral blood monocytes overlap and correlate with lung function.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 3 Downloadable Samples
IlluminaHiSeq2000
Description
When assembling a nephron during development a multipotent stem cell pool becomes restricted as differentiation ensues. A faulty differentiation arrest in this process leads to transformation and initiation of a Wilms'' tumor. Mapping these transitions with respective surface markers affords accessibility to specific cell subpopulations. NCAM1 and CD133 have been previously suggested to mark human renal progenitor populations. Herein, using cell sorting, RNA sequencing, in vitro studies with serum-free media and in vivo xenotransplantation we demonstrate a sequential map that links human kidney development and tumorigenesis; In nephrogenesis, NCAM1+CD133- marks SIX2+ multipotent renal stem cells transiting to NCAM1+CD133+ differentiating segment-specific SIX2- epithelial progenitors and NCAM1-CD133+ differentiated nephron cells. In tumorigenesis, NCAM1+CD133- marks SIX2+ blastema that includes the ALDH1+ WT cancer stem/initiating cells, while NCAM1+CD133+ and NCAM1-CD133+ specifying early and late epithelial differentiation, are severely restricted in tumor initiation capacity and tumor self-renewal. Thus, negative selection for CD133 is required for defining NCAM1+ nephron stem cells in normal and malignant nephrogenesis. Overall design: Human fetal kidney mRNA profiles of 3 cell populations (NCAM1+/CD133-, NCAM+/CD133+, NCAM-/CD133+) were generated by deep sequencing using Illumina HiSeq.
Publication Title
Dissecting Stages of Human Kidney Development and Tumorigenesis with Surface Markers Affords Simple Prospective Purification of Nephron Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples