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GSE15220
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant methylation has been postulated to play an important role in tumorigenesis. We report the use of methylated DNA immunoprecipitation (MeDIP) and whole-genome tiling arrays to investigate methylation changes in testicular germ cell tumor (TGCT) cells. Coupled to expression profiling changes, we found that only 22-26% of differentially methylated genes were also expressed differentially. This phenomenon was independent of the presence of CpG islands in the promoter. Differential methylation and expression of some of these genes were confirmed in testicular tumor tissue. A substantial number of differentially methylated regions in the human genome were not linked to annotated gene loci. Subsequent analysis indicated several microRNAs and small nucleolar RNAs were regulated by these differentially methylated regions. Our results demonstrate the power of the combination of MeDIP-chip analysis and expression profiling for discovery in cancer cells of epigenetically regulated genes and non-coding RNAs in cancer cells.
Publication Title
Genome-wide DNA methylation profiling reveals novel epigenetically regulated genes and non-coding RNAs in human testicular cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 122 Downloadable Samples
Illumina HiSeq 4000
Description
Goblet cell metaplasia and mucus hypersecretion are disabling hallmarks of chronic lung diseases for which no curative treatments are available. Therapies targeting specific upstream drivers of asthma have had variable results. We hypothesized that an a priori-knowledge independent approach would point to new therapies for airway goblet cell metaplasia. We analyzed the transcriptome of an organotypic model of human goblet cell metaplasia. We combined our data with previously published datasets from IL13-exposed in vitro and asthmatic in vivo human airway epithelial cells. The drug perturbation-response connectivity approach identified the heat shock protein 90 (HSP90) inhibitor geldanamycin as a candidate for reverting airway goblet cell metaplasia. We found that geldanamycin not only prevented but reverted IL13-induced goblet cell metaplasia. Geldanamycin did not induce goblet cell death, did not solely block mucin synthesis, and did not block IL13 receptor-proximal signaling. Moreover, the transcriptional effects of geldanamycin were absent in unstimulated cells and became evident only after stimulation with IL13. The predicted mechanism of action suggested that geldanamycin should also revert IL17-induced goblet cell metaplasia, a prediction confirmed by our data. Our findings suggest HSP90 activity may be required for persistence of goblet cell metaplasia driven by various mechanisms in chronic lung diseases. Overall design: For both batches, airway epithelia cultures from the lungs of eight different humans were studied, therefore, there are eight biological replicates. Comparisons should be made within batches. In batch 1 (XAM1), epithelia were exposed to vehicle (DMSO 0.5%), geldanamycin 25 uM, or the HDAC6 inhibitor ISOX 10 uM for 48 hours. In batch 2 (XAM3), the epithelia were exposed to vehicle (DMSO 0.5%), IL13 (20 ng/mL) or IL13 plus geldanamycin (10 uM) for 48 hours.
Publication Title
HSP90 inhibitor geldanamycin reverts IL-13- and IL-17-induced airway goblet cell metaplasia.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of nuclear-enriched miRNAs during mouse granulopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Differentiation of hemopoietic stem cells into granulocytes is characterized by distinct changes in the transcriptome.
Publication Title
Identification of nuclear-enriched miRNAs during mouse granulopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 131 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 71 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These studies adress differential changes in gene expression between sleep deprived and control mice. We profiled gene expression at four time points across the 24H Light/Dark cycle to take into account circadian influences and used three different inbred strains to understand the influence of genetic background.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
These studies adress differential changes in gene expression between 6h sleep deprived and control mice in the brain and the liver. We profiled gene expression in three different inbred strains to understand the influence of genetic background.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To gain insight into the molecular changes of sleep need, this study addresses gene expression changes in a subpopulation of neurons selectively activated by sleep deprivation. Whole brain expression analyses after 6h sleep deprivation clearly indicate that Homer1a is the best index of sleep need, consistently in all mouse strains analyzed. Transgenic mice expressing a FLAG-tagged poly(A)-binding protein (PABP) under the control of Homer1a promoter were generated. Because PABP binds the poly(A) tails of mRNA, affinity purification of FLAG-tagged PABP proteins from whole brain lysates, is expected to co-precipitate all mRNAs from neurons expressing Homer1a. Three other activity-induced genes (Ptgs2, Jph3, and Nptx2) were identified by this technique to be over-expressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness.
Publication Title
Homer1a is a core brain molecular correlate of sleep loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
Control (CRL2429 C11) and A-T (MC3/AT30) iPSC were differentiated according to Erceg et al to generate cerebellar precursors Overall design: Examination of changes in gene expression after a 34 day differentiation protocol in control and A-T iPSC
Publication Title
Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Gene splicing requires three basal genetic elements; the 3’ and 5’ splice sites and the branchpoint to which the 5’ intron termini is ligated to form a closed lariat during the splicing reaction. The 5’ and 3’ splice sites that define exon boundaries have been widely identified, revealing pervasive transcription and splicing of human genes. However, the locations of the third requisite element, the branchpoint, are still largely unknown. Here we employ two complementary approaches, targeted RNA sequencing and exoribonuclease digestion, to distil sequenced reads that traverse the lariat junction and, via non-conventional alignment, locate human branchpoint nucleotides. Alignments identify 88,748 branchpoints that correspond to 20% of known introns, with 76% supported by diagnostic sequence mismatch errors. This affords a first genome-wide analysis of branchpoints, describing their distribution, selection, and the existence of a diverse array of overlapping sequence motifs with distinct usage, evolutionary histories, and co-variation with distal splicing elements. The overlap of branchpoints with noncoding human genetic variation also indicates a notable contribution to disease. This annotation and analysis incorporates branchpoints into transcriptomic research and reflects a core role for this element in the regulatory code that governs gene splicing and expression. Overall design: RNaseR validation of branchpoint nucleotides
Publication Title
Genome-wide discovery of human splicing branchpoints.
Sample Metadata Fields
No sample metadata fields
View Samples