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Homo sapiens
20 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Transciptome analysis using a panel of WM793 melanoma cell lines following stable overexpression of wild-type or mutant forms of human NME1
Publication Title
Identification of a gene expression signature associated with the metastasis suppressor function of NME1: prognostic value in human melanoma.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: CHOP_1.0_ENTREZG (huex10st)
Description
Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.
Publication Title
Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Infection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Publication Title
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Sample Metadata Fields
Specimen part, Treatment
View Samples
GSE52308- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tumors that show evidence of epithelial to mesenchymal transition (EMT) have been associated with metastasis, drug resistance, and poor prognosis. EMT may alter the molecular requirements for growth and survival in different contexts, but the underlying mechanisms remain incomplete. Given the heterogeneity along the EMT spectrum between and within tumors it is important to define the requirements for growth and survival in cells with an epithelial or mesenchymal phenotype to maximize therapeutic efficacy.
Publication Title
Epithelial-to-mesenchymal transition rewires the molecular path to PI3K-dependent proliferation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The goal of this experiment was to explore the molecular network of glucose-TOR signaling in Arabidopsis seedling autotrophic transition stage. We used the whole-genome microarrays to detail the global program of gene expression mediated by glucose and TOR.
Publication Title
Glucose-TOR signalling reprograms the transcriptome and activates meristems.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Mus musculus
- 104 Downloadable Samples
Illumina HiSeq 2000
Description
Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction. Overall design: Endothelium from hypertensive mice were acutely extracted at two different ages (4 weeks and 22 weeks) and compared to endothelium from 22 week old normotensive mice.
Publication Title
Endothelial transcriptomics reveals activation of fibrosis-related pathways in hypertension.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The Hematopoietically-expressed homeobox transcription factor (Hhex) is important for the maturation of definitive hematopoietic progenitors and B-cells during development. We have recently shown that in adult hematopoiesis, Hhex is dispensable for maintenance of hematopoietic stem cells (HSCs) and myeloid lineages but essential for the commitment of Common Lymphoid Progenitors (CLPs) to lymphoid lineages. However, whether Hhex plays a role in HSC self-renewal and myeloid expansion during hematopoietic stress is unknown. Here we show that during serial bone marrow transplantation, Hhex-deleted HSCs are progressively lost, revealing an intrinsic defect in HSC self-renewal. Moreover, Hhex-deleted mice show markedly impaired hematopoietic recovery following myeloablation. In vitro, Hhex-null blast colonies were incapable of replating, implying a specific requirement for Hhex in immature hematopoietic progenitors. Transcriptome analysis of Hhex-null Lin-Sca+Kit+ (LSK) cells showed that Hhex deletion leads to the deregulation of Polycomb Repressive Complex 2 (PRC2) target genes, including an upregulation of Cdkn2a locus, encoding the cell cycle repressors p16Ink4a and p19Arf. Indeed, loss of Cdkn2a restored Hhex-null blast colony replating in vitro, as well as hematopoietic reconstitution following myeloablation in vivo. Thus, HSCs require Hhex to repress Cdkn2a to enable continued self-renewal and response to hematopoietic stress. Overall design: Transcriptional profiling of Hhex-deleted and wild-type LSK cells using RNA sequencing
Publication Title
Hhex Regulates Hematopoietic Stem Cell Self-Renewal and Stress Hematopoiesis via Repression of Cdkn2a.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 744 Downloadable Samples
- Affymetrix Human Gene Expression Array (primeview), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
Disease, Cell line, Treatment
View Samples- Homo sapiens
- 253 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 166 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Genome U133A Array (hgu133a)
Description
Glucocorticoids are universally used in the treatment of acute lymphoblastic leukemia (ALL), and glucocorticoid resistance in leukemia cells confers a poor prognosis. To elucidate mechanisms of glucocorticoid resistance, we determined the prednisolone sensitivity of primary leukemia cells from 444 newly diagnosed ALL patients and found significantly higher expression of caspase 1 (CASP1) and its activator NLRP3 in glucocorticoid resistant leukemia cells, due to significantly lower somatic methylation of CASP1 and NLRP3 promoters. Over-expression of CASP1 resulted in cleavage of the glucocorticoid receptor, diminished glucocorticoid-induced transcriptional response and increased glucocorticoid resistance. Knockdown or inhibition of CASP1 significantly increased glucocorticoid receptor levels and mitigated glucocorticoid resistance in CASP1 overexpressing ALL. Our findings establish a new mechanism by which the NLRP3/CASP1 inflammasome modulates cellular levels of the glucocorticoid receptor and diminishes cell sensitivity to glucocorticoids. The broad impact on glucocorticoid transcriptional response suggests this mechanism could also modify glucocorticoid effects in other diseases.
Publication Title
NALP3 inflammasome upregulation and CASP1 cleavage of the glucocorticoid receptor cause glucocorticoid resistance in leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples