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GSE50451
Homo sapiens
77 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
When using cell lines to study cancer, phenotypic similarity to the original tumor is paramount. Yet, little has been done to characterize how closely Merkel cell carcinoma (MCC) cell lines model native tumors. To determine their similarity to MCC tumor samples, we characterized MCC cell lines via gene expression microarrays. Using whole transcriptome gene expression signatures and a computational bioinformatic approach, we identified significant differences between variant cell lines (UISO, MCC13, and MCC26) and fresh frozen MCC tumors. Conversely, the classic WaGa and Mkl-1 cell lines more closely represented the global transcriptome of MCC tumors. When compared to publicly available cancer lines, WaGa and Mkl-1 cells were similar to other neuroendocrine tumors, but the variant cell lines were not. WaGa and Mkl-1 cells grown as xenografts in mice had histological and immunophenotypical features consistent with MCC, while UISO xenograft tumors were atypical for MCC. Spectral karyotyping and short tandem repeat analysis of the UISO cells matched the original cell line's description, ruling out contamination. Our results validate the use of transcriptome analysis to assess the cancer cell line representativeness and indicate that UISO, MCC13, and MCC26 cell lines are not representative of MCC tumors, whereas WaGa and Mkl-1 more closely model MCC.
Publication Title
Assessment of cancer cell line representativeness using microarrays for Merkel cell carcinoma.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The gene encoding a protein (AmGSTF1) associated with multiple herbicide resistance (MHR) in black-grass was transgenically expressed in Arabidopsis thaliana.The goal of this study was to determine if AmGSTF1 could elicit an MHR phenotype in the transgenic host.
Publication Title
Key role for a glutathione transferase in multiple-herbicide resistance in grass weeds.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Using a combination of cell sorting and microarray analysis, we identified almost 200 genes as having a high level of expression in the notochord.
Publication Title
Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis.
Publication Title
Practical applications of the bioinformatics toolbox for narrowing quantitative trait loci.
Sample Metadata Fields
Sex
View Samples- Danio rerio
- 24 Downloadable Samples
IlluminaHiSeq2500
Description
Damage to and/or loss of sensory neurons can result in debilitating neuropathies that often have a dramatic impact on quality of life. The cellular mechanisms involved in the response of neurons and glia to such pathological insults are poorly understood. Investigation has shown that peripheral glia play critical roles in both the degenerative and regenerative processes that are involved in the responses to peripheral nerve damage. The vast majority of studies have focused primarily on myelinating Schwann cells], with the result that very little is known regarding how the non-myelinating glia that ensheath axons and neuronal somas respond to nerve damage. This is a significant knowledge gap, given that over 80% of cutaneous fibers are unmyelinated, that they transduce such important modalities as itch, pain, temperature, touch and pressure, and that they are affected in many prevalent peripheral neuropathies. It is the goal of this study to shed light on the genetic programs involved in the responses of non-myelinating glia roles to nerve degeneration. We utilized RNA-seq to identify genes that were differentially expressed in the larval head during the process of sensory neuron ablation and axon degeneration in both wild-type larvae and in larvae that do not have peripheral glia (foxd3 mutants) using a selective, conditional approach. Overall, the information regarding differential gene expression in these conditions will provide a basis for further investigation into the cellular processes that underlie pathophysiological responses of neurons and glia to sensory nerve damage. Overall design: mRNA levels were determined using biological triplicate samples from five sets of samples. Three sets from wild-type: control, 2 hrs of metronidazole treatment and 5 hrs of metronidazole treatment. And two sets from foxd3 mutants: control and 5hrs of metronidazole treatment.
Publication Title
Transcriptome Analysis of Chemically-Induced Sensory Neuron Ablation in Zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Bivalent histone domains have been proposed to contribute to pluripotency in embryonic stem cells, suggesting an epigenetic mechanism may regulate stem cell behavior in general. Here we compare histone modifications in two other stem cells derived from the blastocyst. We show that extraembryonic stem cells have little repressive lysine 27 trimethylation and few bivalent domains. Thus, bivalent domains are not a common mechanism for maintaining the undifferentiated state in blastocyst-derived stem cells and alternative mechanisms must mediate transcriptional repression in extraembryonic cells. We show that lysine 9 trimethylation, but not DNA methylation, is likely to fulfill this role. Intriguingly, although we do detect bivalent domains in pluripotent cells in the early mouse embryo, the epigenetic status of extraembryonic cells does not entirely reflect their in vitro stem cell counterparts. Therefore, differences in epigenetic regulation between lineage progenitors in vivo and in vitro may arise during selection for self-renewal in vitro.
Publication Title
Distinct histone modifications in stem cell lines and tissue lineages from the early mouse embryo.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF- superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF- has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF- action in these specialized joints is not known. One of the hurdles to understanding development of IVD is a lack of known markers. To identify genes that are enriched in the developing IVD and to begin to understand the mechanism of TGF- action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in developing vertebrae and IVD. We also compared expression profiles in tissues from wild type and Tgfbr2 mutant mice. Lists of IVD and vertebrae enriched genes were generated. Expression patterns for several genes were verified either through in situ hybridization or literature/ database searches resulting in a list of genes that can be used as markers of IVD. Cluster analysis using genes listed under the Gene Ontology terms multicellular organism development and pattern specification indicated that mutant IVD more closely resembled vertebrae than wild type IVD. We propose TGF- has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF- that warrant further investigation as regulators of IVD development.
Publication Title
Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF- superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF- has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF- action in these specialized joints is not known. To understand the mechanism of TGF- action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in sclerotome cultures treated with TGF- or BMP4. As expected, treatment with BMP4 resulted in up-regulation of cartilage marker genes including Acan, Sox 5, Sox6, and Sox9. In contrast, treatment with TGF-1 did not regulate expression of cartilage markers but instead resulted in up-regulation of many IVD markers including Fmod and Adamtsl2. We propose TGF- has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF- that warrant further investigation as regulators of IVD development.
Publication Title
Molecular profiling of the developing mouse axial skeleton: a role for Tgfbr2 in the development of the intervertebral disc.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The role of microRNAs (miRNA) in first cell fate choice of the preimplantation mouse embryo remains unresolved, as gene expression and knockout data are conflicting. This cell fate choice generates the extraembryonic lineage of the trophoblast and the embryonic lineage of the epiblast (inner cell mass). The trophoblast differentiates into polar and mural cells, where polar cells contribute to placental development and mural cells to the implantation process and Reicherts membrane. The inner cell mass further differentiates into the epiblast and primitive endoderm. We used stem cell lines that can be derived from the trophoblast and epiblast lineages to address the role of miRNAs in early lineage cell fate specification and determination. Using embryonic stem cells (ESC) and trophoblast stem cells (TSC) as starting and ending states of cell development we identified a network of TSC expressed miRNAs that are enriched in ESC targets mRNA. We used constitutive and inducible expression of TSC enriched miRNAs in ESC and show that they can drive cell morphology and gene expression profiles similar to trophoblast. Additionally we show that this process required HDAC2 inhibition and is miRNA specific, as cardiac specific miR-1 could not induce trophoblast under these conditions. In contrast to embryo derived and Cdx2 induced trophoblast cells, miRNAs promote a mural TE like cell phenotype. Transplantation into preimplantation mouse embryos showed that miRNA-induced trophoblast preferentially contributes to the mural trophoblast in both the blastocyst and the Reicherts membrane. Our data support a role for miRNAs and HDACs in the specification of the trophoblast and potentially the polar and mural cell types.
Publication Title
Overexpression of Trophoblast Stem Cell-Enriched MicroRNAs Promotes Trophoblast Fate in Embryonic Stem Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Induction of the transcription factor Sox2 from a doxycycline-inducible promoter in iSox2-DAOY medulloblastoma cells.
Publication Title
Elevating SOX2 levels deleteriously affects the growth of medulloblastoma and glioblastoma cells.
Sample Metadata Fields
Specimen part
View Samples