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Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cyclin C was cloned as a growth-promoting G1 cyclin, and was also shown to regulate gene transcription. Here we report that in vivo cyclin C acts as a haploinsufficient tumour suppressor, by controlling Notch1 oncogene levels. Cyclin C activates an 'orphan' CDK19 kinase, as well as CDK8 and CDK3. These cyclin-C-CDK complexes phosphorylate the Notch1 intracellular domain (ICN1) and promote ICN1 degradation. Genetic ablation of cyclin C blocks ICN1 phosphorylation in vivo, thereby elevating ICN1 levels in cyclin-C-knockout mice. Cyclin C ablation or heterozygosity collaborates with other oncogenic lesions and accelerates development of T-cell acute lymphoblastic leukaemia (T-ALL). Furthermore, the cyclin C encoding gene CCNC is heterozygously deleted in a significant fraction of human T-ALLs, and these tumours express reduced cyclin C levels. We also describe point mutations in human T-ALL that render cyclin-C-CDK unable to phosphorylate ICN1. Hence, tumour cells may develop different strategies to evade inhibition by cyclin C.
Publication Title
Cyclin C is a haploinsufficient tumour suppressor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Insulin resistance represents a hallmark during the development of type 2 diabetes mellitus (T2D) and in the pathogenesis of obesity-associated disturbances of glucose and lipid metabolism 1,2,3. MicroRNA (miR)-dependent posttranscriptional gene silencing has recently been recognized to control gene expression in disease development and progression including that of insulin-resistant T2D. MiRs, whose deregulation alters hepatic insulin sensitivity include miR-143, miR-181 and miR-103/107. Here we report that expression of miR-802 is increased in liver of two obese mouse models and of obese human subjects. Inducible transgenic overexpression of miR-802 in mice causes impaired glucose tolerance and attenuates insulin sensitivity, while reduction of miR-802 expression improves glucose tolerance and insulin action. We identify Hnf1b as a target of miR-802-dependent silencing and shRNA-mediated reduction of Hnf1b in liver causes glucose intolerance, impairs insulin signaling and promotes hepatic gluconeogenesis. In turn, hepatic overexpression of Hnf1b improves insulin sensitivity in db/db mice. Thus, the present study defines a critical role for deregulated expression of miR-802 in the development of obesity-associated impairment of glucose metabolism via targeting Hnf1b and assigns Hnf1b an unexpected role in the control of hepatic insulin sensitivity.
Publication Title
Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
CD133+ and CD133- cells were FACS islated from GBML8 cells to find gene signatures upregulated in cancer stem cells Overall design: After surface immuno staining, CD133+ and CD133- cells were FACS isolated and subjected to RNA isolation. Experiment represent averaged data of 2 independent FACS isolations.
Publication Title
GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Oral squamous cell carcinoma (OSCC) is a prevalent form of cancer that develops from the epithelium of the oral cavity. OSCC is on the rise worldwide, and death rates associated with the disease are particularly high. Despite progress in understanding of the mutational and expression landscape associated with OSCC, advances in deciphering these alterations for the development of therapeutic strategies have been limited. Further insight into the molecular cues that contribute to OSCC is therefore required. Here we show that the transcriptional regulators YAP (YAP1) and TAZ (WWTR1), which are key effectors of the Hippo pathway, drive pro-tumorigenic signals in OSCC. Regions of pre-malignant oral tissues exhibit aberrant nuclear YAP accumulation, suggesting that dysregulated YAP activity contributes to the onset of OSCC. Supporting this premise, we determined that nuclear YAP and TAZ activity drives OSCC cell proliferation, survival, and migration in vitro, and is required for OSCC tumor growth and metastasis in vivo. Global gene expression profiles associated with YAP and TAZ knockdown revealed changes in the control of gene expression implicated in pro-tumorigenic signaling, including those required for cell cycle progression and survival. Notably, the transcriptional signature regulated by YAP and TAZ significantly correlates with gene expression changes occurring in human OSCCs identified by The Cancer Genome Atlas (TCGA), emphasizing a central role for YAP and TAZ in OSCC biology.
Publication Title
A YAP/TAZ-Regulated Molecular Signature Is Associated with Oral Squamous Cell Carcinoma.
Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 6 Downloadable Samples
- NextSeq 500
Description
PTBA has been published to increase renal tubular cell proliferation, increased survival, and increased renal functional recovery in fish and various models of murine models of acute kidney injury. Immunohistological analyses suggested increased cell proliferation is accompanied by increased epithelial-to-mesenchymal transition in the RTECs. In order to elucidate pathways responsible for the increased repair response after compound treatment, larval zebrafish were given AKI and treated with PTBA analogue, UPHD25 or DMSO. Results suggests that epithelial-related genes were downregulated while mesenchymal-related genes were upregulated with injury and compound treatment. Results further validate our immunohistological finding that our compound increase post-AKI repair by increasing EMT in renal tubular cells. Overall design: At 3dpf, larval zebrafish are given acute kidney injury with gentamicin microinjection. 2 days post injury, larvae with AKI are selected and treated with 1uM of PTBA analogue, UPHD25 or vehicle control, 1% DMSO. The fish were treated with UPHD25 or DMSO for 24 hours. Then, pronephric kidneys were collected using DDT, collagenase I, and manual collection. Total 100 larvae were collected per sample, per replicate. Each treatment group was repeated with 3 biological replicates. RNA was collected and sequenced.
Publication Title
Enhancing regeneration after acute kidney injury by promoting cellular dedifferentiation in zebrafish.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples
GSE46923- Homo sapiens
- 139 Downloadable Samples
Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
We screened SLE monocytes from 19 SLE patients and selected 4 that induced CD4+ T cell proliferation in vitro and 4 that did not. CFSE labeled CD4-T cells (105) were incubated with SLE monocytes (2 x 104). Cells were harvested at 6 hours for RNA extraction.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Human Genome U133B Array (hgu133b)
Description
To explore the full extent of IFN-regulated transcriptional changes, we exposed monocytes from two healthy donors to recombinant type I IFN (IFN-2b) in vitro. RNA was extracted at different incubation times (1, 6, 24, 48 and 72 hrs) and the expression data was normalized to that of monocytes cultured with medium.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Time
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
To directly compare the SLE monocyte transcriptional program with that of blood mDC precursors, we purified lineage HLA-DRhighCD11chigh mDCs and CD14+ monocytes from the blood of five healthy donors. Their gene expression profiles were then compared to those of blood SLE monocytes. An unsupervised clustering analysis of transcripts present in >20% of the samples classified healthy monocytes, SLE monocytes and healthy mDCs into three well defined groups. A supervised analysis was then performed to find genes: 1) differentially expressed in healthy mDCs compared to monocytes; 2) shared by healthy blood mDCs and SLE blood monocytes.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133B Array (hgu133b), Affymetrix Human Genome U133A Array (hgu133a)
Description
To better characterize the molecules that could potentially confer antigen presenting capacity to SLE monocytes, we assessed their gene expression profile.
Publication Title
IFN priming is necessary but not sufficient to turn on a migratory dendritic cell program in lupus monocytes.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples