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GSE98156
Arabidopsis thaliana
15 Downloadable Samples
Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
In Arabidopsis, an individually darkened leaf (IDL) initiates senescence much quicker than a leaf from an entirely darkened plant (DP).
Publication Title
Darkened Leaves Use Different Metabolic Strategies for Senescence and Survival.
Sample Metadata Fields
Specimen part
View Samples- Ovis aries
- 4 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Reverse genetics has been widely used to investigate function of viral genes. In the present study we investigated the gene expression profile of a primary ovine cell (OFTu) in response to infection with the wild type (OV-IA82) and deletion mutant virus (OV-IA82024) aiming to determine possible functions for ORFV024 during ORFV infection.
Publication Title
A novel inhibitor of the NF-{kappa}B signaling pathway encoded by the parapoxvirus orf virus.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
We sought to obtain gene signature specific of high oxidative phsophorylation function.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
It has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
It has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.
Publication Title
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Sample Metadata Fields
Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The cellular origin of Ewing tumor (ET), a tumor of bone or soft tissues characterized by specific fusions between EWS and ETS genes, is highly debated. Through gene expression analysis comparing ETs with a variety of normal tissues, we show that the profiles of different EWS-FLI1-silenced Ewing cell lines converge toward that of mesenchymal stem cells (MSC). Moreover, upon EWS-FLI1 silencing, two different Ewing cell lines can differentiate along the adipogenic lineage when incubated in appropriate differentiation cocktails. In addition, Ewing cells can also differentiate along the osteogenic lineage upon long-term inhibition of EWS-FLI1. These in silico and experimental data strongly suggest that the inhibition of EWS-FLI1 may allow Ewing cells to recover the phenotype of their MSC progenitor.
Publication Title
Mesenchymal stem cell features of Ewing tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 50 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Background: Cancer cachexia is a life-threatening metabolic syndrome that causes significant loss of skeletal muscle mass and significantly increases mortality in cancer patients. Currently, there is an urgent need for better understanding of the molecular pathophysiology of this disease, so that effective therapies can be developed. Almost all pre-clinical studies evaluating skeletal muscle’s response to cancer have focused on one or two pre-clinical models, and almost all have focused specifically on limb muscles. In the current study, we reveal key differences in the histology and transcriptomic signatures of a limb muscle and a respiratory muscle in orthotopic pancreatic cancer patient-derived xenograft (PDX) mice. Methods: To create the four cohorts of PDX mice evaluated in this study, tumors resected from four pancreatic ductal adenocarcinoma (PDAC) patients were portioned and attached to the pancreas of immunodeficient NSG mice. Results: Body weight, muscle mass, and fat mass were significantly decreased in each PDX line. Histological assessment of cryosections taken from the tibialis anterior (TA) and diaphragm (DIA) revealed differential effects of tumor-burden on their morphology. Subsequent genome-wide microarray analysis on TA and DIA revealed key differences between their transcriptomes in response to cancer as well. Indeed, upregulated genes in the diaphragm were enriched for extracellular matrix (ECM) protein-encoding genes and genes related to the inflammatory response, and downregulated genes were enriched for mitochondria related protein-encoding genes. Conversely, the TA showed upregulation of canonical atrophy-associated pathways such as ubiquitin-mediated protein degradation and apoptosis and enrichment of downregulated genes encoding ECM proteins. Conclusions: These data suggest that distinct biological processes account for wasting in different skeletal muscles in response to the same tumor burden. Further investigation into these differences will be critical for the future development of effective clinical strategies to counter cancer cachexia.
Publication Title
Distinct cachexia profiles in response to human pancreatic tumours in mouse limb and respiratory muscle.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchip
Description
We demonstrate that Prnp dosage is critical for the maintenance of neuronal homeostasis since both its absence and, more relevantly, its overexpression induce higher sensitivity to kainate (KA) damage. These data correlate with electrophysiological results in freely behaving mutant mice showing an imbalance in activity-dependent synaptic processes, as determined from input/output curves, paired-pulse facilitation, and LTP studies. Gene expression profiling showed that 129 genes involved in canonical pathways such as Ubiquitination or Neurotransmission among others were co-regulated in knockout and PrPc overexpressing mice. RT-qPCR analysis of neurotransmission-related genes confirmed GABA-A and AMPA-Kainate receptor subunit transcriptional co-regulation in both Prnp -/- and Tg20 mice. Our results demonstrate that PrPc is necessary for the proper homeostatic functioning of hippocampal circuits, because of its interactions with GABAA and AMPA-Kainate receptors.
Publication Title
Regulation of GABA(A) and glutamate receptor expression, synaptic facilitation and long-term potentiation in the hippocampus of prion mutant mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Serum levels of interleukin-8 (IL-8) are increased in the serum of people with pancreatic cancer and associated with the loss of body weight and low muscle mass. We have identified that systemic (intraperitoneal) injection of IL-8 into mice induces significant skeletal muscle atrophy. Transcriptional profiling of muscle harvested from these same mice identified the genes and biological processes associated with this IL-8 induced atrophy including gene clusters related to chromatin modification, muscle cell differentiation, and ubiquitin ligase complex.
Publication Title
IL-8 Released from Human Pancreatic Cancer and Tumor-Associated Stromal Cells Signals through a CXCR2-ERK1/2 Axis to Induce Muscle Atrophy.
Sample Metadata Fields
Treatment
View Samples