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SRP032812
Homo sapiens
20 Downloadable Samples
IlluminaHiSeq2000
Description
Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome profiling in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (=3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type-specific genes; and (iii) GWAS variants associated with traits relevant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type-specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases. Overall design: Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project. NISC Comparative Sequencing Program
Publication Title
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The study was designed to identify the molecular changes that occur in EGFR mutant NSCLCs that become resistant to TKI by transforming to SCLC.
Publication Title
RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
mRNA profiling of mouse ureters comparing wild-type ureter vs. ureters from mice having whole body deletion of miR-143 and miR-145 which results in abnormal ureter peristalsis and hydronephrosis
Publication Title
Deletion of the miR-143/145 cluster leads to hydronephrosis in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2500
Description
Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic. Overall design: Examination of mRNA levels of PC9 parental, drug-tolerant, PC9-GR2 and PC9-GR3 cells after treatment with vehicle, gefitinib or WZ4002 for 24 hours.
Publication Title
Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
mRNA profiling of mouse kidney preglomerular arterioles comparing wild type arterioles vs.arterioles from mice having deletion of RBP-J in cells of the renin lineage
Publication Title
Recombination signal binding protein for Ig-κJ region regulates juxtaglomerular cell phenotype by activating the myo-endocrine program and suppressing ectopic gene expression.
Sample Metadata Fields
Sex, Age
View Samples- Rattus norvegicus
- 158 Downloadable Samples
- IlluminaHiSeq2000
Description
Pineal function follows a 24-hour schedule, dedicated to the conversion of night and day into a hormonal signal, melatonin. In mammals, 24-hour changes in pineal activity are controlled by a neural pathway that includes the central circadian oscillator in the suprachiasmatic nucleus and the superior cervical ganglia (SCG), which innervate the pineal gland. In this study, we have generated the first next-generation RNA sequencing evidence of neural control of the daily changes in the pineal transcriptome. We found over 3000 pineal transcripts that are differentially expressed (p <0.001) on a night/day basis (70% of these genes increase at night, 376 with fold change >4 or <1/4), the majority of which had not been previously identified as such. Nearly all night/day differences were eliminated by neonatal removal or decentralization of the SCG, confirming the importance of neural input for differential night/day changes in transcript abundance. In contrast, very few non-rhythmic genes showed evidence of changes in expression due to the surgical procedure itself, which is consistent with the hypothesis that post neonatal neural stimulation is not required for cell fate determination and maintenance of phenotype. Many of the transcripts that exhibit marked differential night/day expression exhibited similar changes in response to in vitro treatment with norepinephrine, the SCG neurotransmitter which mediates pineal regulation. Similar changes were also seen following treatment with an analog of the norepinephrine second messenger, cyclic AMP. Overall design: For the in vivo data, there were 8 biological conditions: day and night time points for each of four surgical groups: Control (Ctrl) Sham-surgery (Sham), Decentralized (DCN), and Ganglionectomized (SCGX). Samples were pooled into three biological replicates for each biological condition. For the in vitro data there were 3 biological conditions: Untreated control (CN), DBcAMP-treated (DB), and Norepinephrine-treated (NE). For the pineal enrichment comparison, three samples (i.e. no biological replicates) were used: pineal-day, pineal-night and mixed-tissue. For the mixed tissues sample, the following tissues from three rats sacrificed at ZT7 were used: cortex, cerebellum, midbrain, hypothalamus, hindbrain, spinal cord, retina, pituitary, heart, liver, lung, kidney, skeletal muscle, small intestine, adrenal gland. Total RNA was extracted from each tissue, and then equal amounts of each of the 15 tissues were combined for the final pooled sample.
Publication Title
Neurotranscriptomics: The Effects of Neonatal Stimulus Deprivation on the Rat Pineal Transcriptome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
These datasets describe a melanocyte specific, HIF1A-Dependent / Hypoxia-Responsive gene expression signature defined by the regulation of genes critical to metabolism, chromatin and transcriptional regulation, vascularization and cellular invasivness. These genes provide lineage specific targets for refinement of diagnostic markers associated with primary melanoma tumor metastatic potential, and also provides novel molecular targets for therapeutic strategies targeting metastatic disease progression.
Publication Title
Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Local renin antiotensin systems have been identified for many extra-renal sites. Bone marrow has been proposed as one such site, although the nature of the renin-expressing cell type(s) has not been established.
Publication Title
Identification of renin progenitors in the mouse bone marrow that give rise to B-cell leukaemia.
Sample Metadata Fields
Specimen part
View Samples