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GSE109567
Bos taurus
12 Downloadable Samples
Bovine Gene 1.0 ST Array (bovgene10st)
Description
The innate repair and regeneration potential of skeletal tissues such as the intervertebral disc and articular cartilage is extremely limited, in part due to their avascularity and low cell density. Despite recent advances in MSC-based disc and cartilage regeneration, key challenges remain, including the sensitivity of these cells to in vivo microenvironmental stress such as low oxygen and nutrient levels. The objective of this study was to investigate whether preconditioning with hypoxia and/or transforming growth factor-beta (TGF-) can enhance MSC survival and extracellular matrix production in a low oxygen and nutrient-limited microenvironment. Secondarily, the effects of donor variability on the response of MSCs to preconditioning was examined. MSCs from multiple bovine donors were preconditioned in monolayer in normoxia or hypoxia, with or without TGF-.
Publication Title
Hypoxic Preconditioning Enhances Bone Marrow-Derived Mesenchymal Stem Cell Survival in a Low Oxygen and Nutrient-Limited 3D Microenvironment.
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Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Elevated branched chain amino acids (BCAAs) are associated with obesity and insulin resistance. How long-term dietary BCAAs impact late-life health and lifespan is unknown. Here, we show that when dietary BCAAs are varied against a fixed, isocaloric macronutrient background, long-term exposure to high BCAA diets led to hyperphagia, obesity and reduced lifespan. These effects were not due to elevated BCAA per se or hepatic mTOR activation, but rather the shift in balance between dietary BCAAs and other AAs, notably tryptophan and threonine. Increasing the ratio of BCAAs to these AAs resulted in hyperphagia and was linked to central serotonin depletion. Preventing hyperphagia by calorie restriction or pair-feeding averted the health costs of a high BCAA diet. Our data highlight a role for amino acid quality in energy balance and show that health costs of chronic high BCAA intakes were not due to intrinsic toxicity; rather, to hyperphagia driven by AA imbalance. Overall design: 3 animals per sex per diet were used. Mice were fed one of four diets (all 19% total protein, 63% carbohydrate, 18% fat, total energy density 14 kJ/g) varying in BCAA content (BCAA200: twice BCAA content of control diet AIN93G; BCAA100: standard content of BCAAs; and BCAA50 and BCAA20: containing one half and one fifth of standard content of BCAAs), and either euthanized at 15 months of age or maintained for determination of lifespan.
Publication Title
Branched chain amino acids impact health and lifespan indirectly via amino acid balance and appetite control.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Steroid hormone receptors are simultaneously active in many tissues and capable of altering each other's function. Estrogen receptor ? (ER) and glucocorticoid receptor (GR) are expressed in the uterus and their ligands have opposing effects on uterine growth. In endometrial tumors expressing high levels of ER, we surprisingly found that expression of GR is associated with poor prognosis. Dexamethasone reduced normal uterine growth in vivo; however, this growth inhibition was abolished in estrogen-induced endometrial hyperplasia. We observed low genomic binding site overlap when ER and GR are induced with their respective ligands; however, upon simultaneous induction they co-occupy more sites. GR binding is significantly altered by estradiol with GR recruited to ER bound loci that become more accessible upon estradiol induction. Gene expression responses to co-treatment were more similar to estradiol, but with novel regulated genes. Our results suggest phenotypic and molecular interplay between ER and GR in endometrial cancer. Overall design: ChIP-seq, ATAC-seq, and RNA-seq data collected from endometrial cancer cell lines induced with dexamethasone, estradiol, or the combination
Publication Title
FFPEcap-seq: a method for sequencing capped RNAs in formalin-fixed paraffin-embedded samples.
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Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 21 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Analysis of undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma-like tumors from LSL-KrasG12D, p53Fl/Fl mouse model of soft tissue sarcoma.
Publication Title
Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 27 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The cell of origin for rhabdomyosarcoma (RMS) and undifferentiated pleomorphic sarcoma (UPS) remains to be determined. We utilized two skeletal muscle specific inducible Cre mouse lines to transform both skeletal muscle stem cells and progenitors to determine which cells give rise to RMS and UPS.
Publication Title
Distinct and overlapping sarcoma subtypes initiated from muscle stem and progenitor cells.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 72 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Formaldehyde (FA), an endogenous cellular aldehyde, is a rat nasal carcinogen. In this study, concentration- and exposure-duration transitions in FA mode of action (MOA) were examined with pharmacokinetic (PK) modeling for tissue formaldehyde acetal (FAcetal) and glutathione (GSH) and with histopathology and gene expression studies for tissue responses in nasal epithelium from rats exposed to 0, 0.7, 2, 6, 10 or 15 ppm FA 6 hr/day for 1, 4 or 13 weeks. The study had two goals. The first goal was to develop a basic PK model to estimate various forms of tissue formaldehyde and tissue glutathione (GSH). The second goal was to compare histopathology and gene expression changes in nasal tissues caused by inhalation of FA with changes in tissue FAcetal and free GSH calculated from the PK model. Patterns of gene expression varied with concentration and with duration. At 0.7 and 2 ppm, sensitive response genes (SRGs) - associated with cellular stress, thiol transport/reduction, inflammation, and cell proliferation - were similarly upregulated at all exposure durations. At 6 ppm and greater, gene expression changes showed enrichment of pathways involved in cell cycle, DNA repair, and apoptosis processes. ERBB, EGFR, WNT, TGF-, Hedgehog, and Notch signaling were also enriched in differentially expressed genes. Benchmark doses (BMDs) for genes in significantly enriched pathways were lower at 13 weeks than at 1 or 4-week. The transcriptional and histological changes corresponded to PK model-predicted changes in free GSH at 0.7 and 2 ppm and in FAcetal at 6 ppm. DNA-replication stress, enhanced proliferation, metaplasia, and stem cell-niche activation appear to be associated with FA carcinogenesis at 6 ppm and above. Dose dependencies in MOA, the presence of high physiological FAcetal, and non-linear FAcetal/GSH tissue kinetics indicate that FA concentrations below 150 ppb (and probably any concentrations below irritant levels, i.e., ~ 1 ppm) would not increase cancer risks of inhaled FA in the nose or any other tissue. Closer examination of dose response relationships for endogenous compound toxicity could help guide biologically relevant approaches for chemical risk assessment.
Publication Title
Formaldehyde: integrating dosimetry, cytotoxicity, and genomics to understand dose-dependent transitions for an endogenous compound.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Apoptosis is deregulated in most, if not all, cancers, including hematological malignancies. In this study, we wanted to test whether primary acute myeloid leukemia (AML) samples are sensitive for inhibitor of apoptosis (IAP) protein antagonist treatment in vitro, and which AML subgroup might profit most from such a novel therapeutic strategy. We treated diagnostic samples of 67 adult AML patients with either cytarabine (ara-C) or IAP antagonist BV6 and correlated sensitivity with clinical, cytogenetic and molecular markers, and expression levels of selected genes involved in apoptosis. Primary AML samples showed differential sensitivity to treatment with either ara-C (40% sensitive, 17% intermediate, 43% resistant) or BV6 (51% sensitive, 21% intermediate, 28% resistant). Notably, 69% of ara-C resistant samples showed a good to fair response to IAP inhibition. Furthermore, combination treatment of ara-C with BV6 showed additive effects in most samples. Differences in sensitivity to IAP antagonist treatment correlated with significantly elevated expression levels of TNF and lower levels of XIAP in BV6 sensitive samples, as well as with NPM1 mutations. Gene expression profiling pointed to apoptosis-related pathways, which were specifically induced by IAP inhibition in sensitive samples. Thus, our results suggest IAP inhibition as a potential novel therapeutic option in AML.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 23 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
The purpose of this study was to characterise the effects of trastuzumab and pertuzumab, either as single agents or as combination therapy on gene and protein expression in human ovarian cancer in vivo. Illumina BeadChips were used to profile the transcriptome after four days treatment of SKOV3 tumor xenografts. Although genes involved with HER2, MAP-kinase and p53 signaling pathways were commonly induced by all treatments, a greater number and variety of genes were differentially expressed by the complementary combination therapies compared to either drug on its own. The protein level of the CDK-inhibitors p21 and p27 were increased in response to both agents alone and further by the combination; pERK signaling was inhibited by all treatments; but only pertuzumab alone inhibited pAkt signaling. The expression of proliferation, apoptosis, cell division and cell cycle markers was distinct in a panel of primary ovarian cancer xenografts, suggesting heterogeneity of response in ovarian cancer and the need to establish biomarkers of response.
Publication Title
Defining the molecular response to trastuzumab, pertuzumab and combination therapy in ovarian cancer.
Alternate Accession IDs
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Inhibitor of apoptosis (IAP) proteins are expressed at high levels in CLL cells and may contribute to evasion of cell death leading to poor therapeutic outcome. Of note, prognostic unfavourable cases with e.g. non-mutated VH-status and TP53 mutation responded significantly better to BV6 than samples with unknown or favourable prognosis e.g. 13q deletion. The majority of cases with 17p deletion (10/12) and Fludarabine refractory cases were sensitive to BV6, indicating that BV6 acts independently of the p53 pathway. Importantly, BV6 dose-dependently induced cell death in 28 of 51 (54%) investigated patient samples while B cells from healthy donors were largely unaffected. BV6 also triggered cell death under survival conditions mimicking the microenvironment e.g. by adding CD40 ligand or in conditioned medium. Gene expression profiling identified cell death- and NF-kB-signaling among the top pathways regulated by BV6. This was confirmed by data showing that BV6 causes degradation of cIAP1 and cIAP2 and NF-kB pathway activation. BV6 induced cell death depended on production of reactive oxygen species, since addition of ROS scavengers significantly rescued BV6-triggerd cell death. In contrast, BV6 induced cell death independently of caspase activity, RIP1 activity or TNF-alpha, since zVAD.fmk, necrostatin-1 or TNF-alpha-blocking antibody Enbrel failed to protect against cell death. Of note, transcripts of ROS regulatory proteins were modulated by BV6. Thus, these data have important implications for developing new therapeutic strategies to overcome cell death resistance in CLL especially in poor prognostic subgroups.
Publication Title
Targeting inhibitor of apoptosis proteins by Smac mimetic elicits cell death in poor prognostic subgroups of chronic lymphocytic leukemia.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Treatment
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Analysis of differential gene expression for rutured vs stable abdominal aortic aneurysms (AAA) and for intermediate size (55mm) vs large (>70mm) AAA.
Publication Title
Molecular Fingerprint for Terminal Abdominal Aortic Aneurysm Disease.
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Sample Metadata Fields
Specimen part
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