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Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
TDP-43 is an RNA/DNA-binding protein implicated in transcriptional repression and mRNA processing. Inclusions of TDP-43 are hallmarks of frontotemporal dementias and amyotrophic lateral sclerosis. Besides aggregation of TDP-43, loss of nuclear localization is observed in disease. To identify relevant targets of TDP-43, we performed an expression profiling study. Thereby, histone deacetylase 6 (HDAC6) downregulation was discovered upon TDP-43 silencing on mRNA and protein level in human embryonic kidney HEK293E and neuronal SH-SY5Y cells. This was accompanied by accumulation of the major HDAC6 substrate, acetyl-tubulin. Expression of wild-type but neither RNA-binding- nor nuclear-localization-deficient TDP-43 restored HDAC6 expression. Moreover, TDP-43 bound specifically to HDAC6 mRNA arguing for a direct functional interaction. Importantly, in vivo validation in TDP-43 knockout Drosophila melanogaster also showed HDAC6 mRNA decrease. HDAC6 is necessary for protein aggregate formation and degradation. Indeed, downregulation of HDAC6 reduced aggregate formation and increased cytotoxicity of expanded poly-glutamine ataxin-3 in TDP-43 silenced cells. This was completely restored by co-transfection with HDAC6. In conclusion, loss of functional TDP-43 causes HDAC6 downregulation and might thereby contribute to pathogenesis.
Publication Title
Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Canonical IKK/NF-B signaling is a master regulator of inflammation and innate immunity and has been implicated in the pathogenesis of T1D. To investigate the impact of NF-B activation on -cell homeostasis and diabetes development, we generated a transgenic gain-of-function mouse model allowing conditional NF-B activation via expression of IKK2-CA (constitutively active IKK2 allele) in -cells using the tetracycline-regulated gene expression system. Pdx-1-tTA (knockin model generating Pdx-1 haploinsufficiency) driver mice were used for -cell specific transgene expression. Double transgenic IKK2-CA-pdx-1 mice develop a full-blown immune-mediated diabetes.To identify gene expression changes underlying this diabetes development pancreatic islets of diabetic IKK2-CA-Pdx-1, PDX-1 +/- and control mice were prepared and isolated total RNA was used for microarray analysis.
Publication Title
Long-term IKK2/NF-κB signaling in pancreatic β-cells induces immune-mediated diabetes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The MYC oncogene, which is commonly mutated/amplified in tumors, represents an important regulator of cell growth owing to its ability to induce both proliferation and apoptosis. Recent evidence links MYC to altered miRNA expression, thereby suggesting that MYC-regulated miRNAs might contribute to tumorigenesis. To further analyze the impact of MYC-regulated miRNAs we investigated a murine lymphoma model harboring the MYC transgene in a Tet-off system in order to control its expression. Microarray-based miRNA expression profiling revealed both known and novel MYC targets. Among the miRNAs repressed by MYC we identified the potential tumor suppressor miR-26a, which possessed the ability to attenuate proliferation in MYC-dependent cells. Interestingly, miR-26a was also found to be deregulated in primary human Burkitt lymphoma samples, thereby likely being of clinical relevance. While today only few miRNA targets have been identified in human disease, we could show that ectopic expression of miR-26a influenced cell cycle progression by targeting the bona fide oncogene EZH2, a Polycomb protein and global regulator of gene expression yet unknown to be regulated by miRNAs. Thus, in addition to directly targeting protein-coding genes, MYC modulates genes important to oncogenesis via deregulation of miRNAs, thereby vitally contributing to MYC-induced lymphomagenesis.
Publication Title
MYC stimulates EZH2 expression by repression of its negative regulator miR-26a.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Glioblastoma cells are characterized by a highly invasive behavior whose mechanisms are not yet understood. Using the wound healing and Boyden chamber assays we compared in the present study the migration and invasion abilities of 5 glioblastoma cell lines (DK-MG, GaMG, U87-MG, U373-MG, SNB19) differing in p53 and PTEN status. We also analyzed by Western blotting the expression of PTEN, p53, mTOR and several other marker proteins involved in cell adhesion, migration and invasion. Among 5 cell lines, GaMG cells exhibited the fastest rate of wound closure, whereas U87-MG cells showed the most rapid chemotactic migration in the Boyden chamber assay. In DK-MG and GaMG cells, F-actin mainly occurred in the numerous stress fibers spanning the cytoplasm, whereas U87-MG, U373-MG and SNB19 cells preferentially expressed F-actin in filopodia and lamellipodia. Moreover, the two glioblastoma lines mutated in both p53 and PTEN genes (U373-MG and SNB19) were found to exhibit the fastest invasion rates through the Matrigel matrix.
Publication Title
Actin cytoskeleton organization, cell surface modification and invasion rate of 5 glioblastoma cell lines differing in PTEN and p53 status.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 1 Downloadable Sample
NextSeq 500
Description
This dataset consists of single-cell RNA-seq (Drop-seq) data from thymi of day 14.5 mouse embryos. The sample includes the whole thymus, including mesenchyme, endothelium, epithelium, thymocytes, and other lymphocytes. The mouse is a Rag2-/- knockout. Overall design: 1 sample
Publication Title
Inferring population dynamics from single-cell RNA-sequencing time series data.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE38961- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder caused by mutations in the transforming growth factor (TGF-) receptors TGFBR1 or TGFBR2. Most patients with LDS develop severe aortic aneurysms resulting in early need of surgical intervention. We investigated circulating outgrowth endothelial cells (OEC) from the peripheral blood of LDS to gain further insight into the pathophysiology of the disorder. We performed gene expression profiling using microarray analysis followed by quantitative PCR for verification of gene expression. OECs isolated from age- and sex-matched healthy donors served as reference control.
Publication Title
Overexpression of Gremlin-1 in patients with Loeys-Dietz syndrome: implications on pathophysiology and early disease detection.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Saccharomyces cerevisiae
- 22 Downloadable Samples
- Illumina Genome Analyzer II
Description
We combined the nuclear run-on (NRO) assay which labels and captures nascent transcripts with high throughput DNA sequencing to examine transcriptional activity in Saccharomyces cerevisiae. Overall design: Examination of nascent transcripts and steady-state transcripts in exponentially growing and heat-shock treated yeast.
Publication Title
Genome-Wide Analysis of Nascent Transcription in Saccharomyces cerevisiae.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Gallus gallus
- 20 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
To investigate the role of AP-1 in Src-mediated transformation, we undertook a gene profiling study to characterize the transcriptomes of v-Src-transformed CEF expressing either the c-Jun dominant-negative mutant TAM67 or JunD shRNA.
Publication Title
JunD/AP-1 Antagonizes the Induction of DAPK1 To Promote the Survival of v-Src-Transformed Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: To determine the effects of age and topographic location on gene expression in human neural retina.
Publication Title
Effects of aging and anatomic location on gene expression in human retina.
Sample Metadata Fields
Sex, Age
View Samples