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Pan troglodytes, Homo sapiens
355 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Lymphoblastoid cell lines (LCLs), originally collected as renewable sources of DNA, are now being used as a model system to study genotype-phenotype relationships in human cells. These cell lines have been used to search for genetic variants that are associated with drug response as well as with more basic cellular traits such as RNA levels. In setting out to extend such studies by searching for genetic variants contributing to drug response, we observed that phenotypes in LCLs were, in our lab and others, significantly affected by experimental confounders (i.e. in vitro growth rate, metabolic state, and relative levels of the Epstein-Barr virus used to transform the cells). As we did not find any SNPs associated with genome-wide significance to drug response, we evaluated whether incorporating RNA expression levels (and eQTLs) in the analysis could increase power to detect such effects. As previously shown, cis-acting eQTLs were detectable for a sizeable fraction of RNAs and baseline levels of many RNAs predicted response to several drugs. However, we found only limited evidence that SNPs influenced drug response through their effect on expression of RNA. Efforts to use LCLs to map genes underlying cellular traits will require great care to control experimental confounders, unbiased methods for integrating and interpreting such multi-dimensional data, and much larger sample sizes than have been applied to date.
Publication Title
Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Expression analysis from two genetically engineered mouse models of osteosarcoma determine the expression profile of mouse osteosarcoma Human osteosarcoma (OS) is comprised of three different subtypes: fibroblastic, chondroblastic and osteoblastic. We previously generated a mouse model of fibroblastic OS by conditional deletion of p53 and Rb in osteoblasts. Here we report an accurate mouse model of the osteoblastic subtype using shRNA-based suppression of p53. Like human OS, tumors frequently present in the long bones and preferentially disseminate to the lungs; features less consistently modeled using Cre:lox approaches. Our approach allowed direct comparison of the in vivo consequences of targeting the same genetic drivers using different technology. This demonstrated that the effects of Cre:lox and shRNA mediated knock-down are qualitatively different, at least in the context of osteosarcoma. Through the use of complementary genetic modification strategies we have established a model of a distinct clinical subtype of OS that was not previously represented and more fully recapitulated the clinical spectrum of this human tumor.
Publication Title
Modeling distinct osteosarcoma subtypes in vivo using Cre:lox and lineage-restricted transgenic shRNA.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Comparison of two Chlamydia-specific CD4 T cells that are dependent on iNOS to terminate Chlamydia replication in epithelial cells to two Chlamydia-specific CD4 T cells that are iNOS-independent: Chlamydia trachomatis urogenital serovars replicate predominately in epithelial cells lining the reproductive tract. This tissue tropism poses a unique challenge for the host immune system and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical and sufficient to clear primary genital tract infections. In vitro studies have shown that CD4 T cells terminate the infection in epithelial cells by up regulating epithelial iNOS transcription and nitric oxide production via IFN-gammaand T cell-epithelial cell interactions mediated by LFA-1-ICAM-1. This mechanism however is not critical as iNOS-deficient mice clear infections normally, and IFN-gamma deficient mice clear 99.9% of the infection with near normal kinetics. We recently showed that a subset of Chlamydia-specific CD4 T cell clones were able to terminate replication in epithelial cells using a mechanism that was independent of iNOS and IFN-gamma. That mechanism did not require physical lysis of infected cells, but instead required T cell degranulation. In this study we advanced that work using gene expression microarrays to compare CD4 T cell clones that are able to terminate epithelial replication via an iNOS-independent mechanism to iNOS-dependent CD4 T cell clones. Micro array experiments showed that Plac8 was differentially expressed by the T cell clones having the iNOS-independent mechanism. Plac8-deficient mice had significantly delayed clearance of C. muridarum genital tract infections, and that the large majority of Plac8-deficient mice treated with the iNOS-inhibitor N-monomethyl-L-arginine (MLA) were unable to resolve a C. muridarum genital tract infection over 8 weeks. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections; one mechanism dependent on iNOS, the other mechanism dependent on Plac8. While T cells subsets have been defined by cytokine profiles, there are important subdivisions by effector functions, in this case CD4Plac8.
Publication Title
Plac8-dependent and inducible NO synthase-dependent mechanisms clear Chlamydia muridarum infections from the genital tract.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 44 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
The self-renewal and differentiation capacities of human pluripotent stem cells (hPSCs) make them good sources of cells for cell transplantation therapy, drug development, and studies of cellular differentiation and development. However, the large numbers of cells necessary for many of these applications require extensive expansion of hPSC cultures, a process that has been associated with applications require extensive expansion of hPSC cultures, a process that has been associated with genetic and epigenetic alterations. We have performed a systematic study over more than 100continuous passages to identify characteristics of culture conditions (including passage method, substrate, and media type) that influence the genetic and epigenetic stability and the phenotypic characteristics of hPSCs. The predominant effects we observed were increased genetic instability with enzymatic passage, higher cell proliferation with feeder-free substrate, and variations among cultures in global gene expression and DNA methylation with time in culture. We observed recurrent duplications in two genomic regions that have been noted in earlier studies to be hotspots for duplication in hPSCs, as well as a previously unreported recurrent deletion of the tumor suppressor gene TP53 in all but one of the long-term culture conditions; the exception was the condition using mechanical passaging on feeder layers. The deletion of TP53 is associated with decreased mRNA expression of TP53, as well as alterations in the expression of several other genes in the TP53 pathway, which taken together indicate a decrease in the function of the TP53 pathway. Our results highlight the need for careful assessment of effects of culture conditions on cells intended for clinical therapies.
Publication Title
Increased risk of genetic and epigenetic instability in human embryonic stem cells associated with specific culture conditions.
Sample Metadata Fields
Sex, Cell line
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line, Subject
View Samples- Homo sapiens
- 48 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting, and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.
Publication Title
Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Intervertebral disc degeneration is an important contributor to chronic low back pain. While a wide spectrum of clinically relevant degenerative disc phenotypes have been observed during aging, their molecular underpinning have not been established.
Publication Title
Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging.
Sample Metadata Fields
Age, Specimen part
View Samples
GSE75789- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors. Despite radical surgery and radiotherapy supported by chemotherapy, the disease still remains incurable with extremely low median survival rate of 12-15 months from the time of initial diagnosis. The main cause of treatment failure is considered to be the presence of cells that are resistant to such treatment. MicroRNAs (miRNAs) as regulators of gene expression are involved in the tumor pathogenesis, including GBM. MiR-338 is a brain specific miRNA which has been described to target pathways involved in proliferation and differentiation. In our study, miR-338-3p and -5p were differentially expressed in GBM tissue in comparison to non-tumor brain tissue. Overexpression of miR-338-3p with miRNA mimic did not show any changes in proliferation rates in GBM cell lines (A172, T98G, U87MG). On the other hand, pre-miR-338-5p notably decreased proliferation and caused cell cycle arrest. Since radiation is currently the main treatment modality in GBM, we combined overexpression of pre-miR-338-5p with radiation, which led to significantly decreased of cell proliferation, and increased cell cycle arrest and apoptosis in comparison to only irradiated cells. To better elucidate the mechanism of action, we performed gene expression profiling analysis that revealed targets of miR-338-5p being Ndfip1, Rheb, ppp2R5a. These genes have been described to be involved in DNA damage response, proliferation and cell cycle regulation. To our knowledge, this is the first study to describe role of miR-338-5p in GBM and its potential to improve sensitivity of GBM to radiation.
Publication Title
MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 129 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Analysis of biopsy hippocampal tissue of patients with pharmacoresistant temporal lobe epilepsy (TLE) undergoing neurosurgical removal of the epileptogenic focus for seizure control. Chronic TLE goes along with focal hyperexcitability. Results provide insight into molecular mechanisms that may play a role in seizure propensity
Publication Title
Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus.
Sample Metadata Fields
Specimen part
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