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GSE3059
Homo sapiens
32 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background---For decades, plasma lipid levels have been known risk factors of atherosclerosis. Recently, inflammation has gained acceptance as a crucial event in the pathogenesis and development of atherosclerosis. A number of studies have provided some insights into the relationships between the two aspects of atherosclerosis: plasma lipids --- the risk factors, and circulating leukocytes --- the effectors of inflammation. In this study, we investigate the relationships between plasma lipids and leukocytes.
Publication Title
Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Transcriptome analysis of total RNA samples from human cell line (LAM 621-101, female)
Publication Title
Post-transcriptional Regulation of De Novo Lipogenesis by mTORC1-S6K1-SRPK2 Signaling.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
The combined influence of oncogenic drivers, genomic instability, and/or DNA damage repair deficiencies increases replication stress in cancer. Cells with high replication stress rely on the upregulation of checkpoints like those governed by CHK1 for survival. Previous studies of the CHK1 inhibitor prexasertib demonstrated activity across multiple cancer types. Therefore, we sought to (1) identify markers of prexasertib sensitivity and (2) define the molecular mechanism(s) of intrinsic and acquired resistance using preclinical models representing multiple tumor types. Our findings indicate that while cyclin E dysregulation is a driving mechanism of prexasertib response, biomarkers associated with this aberration lack sufficient predictive power to render them clinically actionable for patient selection. Transcriptome analysis of a pan-cancer cell line panel and in vivo models revealed an association between expression of E2F target genes and prexasertib sensitivity and identified innate immunity genes associated with prexasertib resistance. Functional RNAi studies supported a causal role of replication fork components as modulators of prexasertib response. Mechanisms which protect cells from oncogene-induced replication stress may safeguard tumors from such stress induced by a CHK1 inhibitor, resulting in acquired drug resistance. Furthermore, resistance to prexasertib may be shaped by innate immunity.
Publication Title
A pan-cancer transcriptome analysis identifies replication fork and innate immunity genes as modifiers of response to the CHK1 inhibitor prexasertib.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 25 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We used microarrays to determine the effect of prenatal nicotine exposure on gene expression profiles in the striatum of adolescent rats. We found a number of immediate early genes to be differentially expressed due to food-restriction.
Publication Title
Long-term effects of gestational nicotine exposure and food-restriction on gene expression in the striatum of adolescent rats.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
Illumina HiSeq 3000
Description
Colorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R) but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited and the few remaining tumors were of low grade dysplasia. RNA-Seq analysis demonstrated downregulation of STAT3 and Wnt pathway components. Since EGF-R on myeloid cells, but not on intestinal epithelial cells is required for intestinal cancer and IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6 signaling. Tumor formation was equally inhibited in IL-6 -/- and sgp130Fc transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated. ADAM17 is needed for EGF-R-mediated induction of IL-6 synthesis, which via IL-6 trans-signaling induces ß-catenin dependent tumorigenesis. Our data reveal the possibility of a novel strategy for treatment of colorectal cancer, which could circumvent intrinsic and acquired resistance to EGF-R blockade. Overall design: RNA sequencing of tumor tissue and surrounding unaffected tissue of Apc Min/+ and Apc Min/+ ::ADAM17 ex/ex
Publication Title
ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells (strain L) and cultured.
Publication Title
Genetic and transcriptional evolution alters cancer cell line drug response.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To compare human memory CD4+ T cell subsets in peripheral blood (PB) and bone marrow (BM) of healthy individuals at transcriptional level, we analyzed the global gene expression of ex vivo PB CD69- as well as BM CD69- and CD69+ memory CD4+ T cells from 4 paired PB and BM samples. The gene expression of these subsets was additionally compared to the transcriptional profile of 8 PB samples taken ex vivo or stimulated with phorbol myristate acetate (PMA) and Ionomycin for 3 hours.
Publication Title
Human memory T cells from the bone marrow are resting and maintain long-lasting systemic memory.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 18 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
Publication Title
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 18 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
When C. elegans larvae hatch in the absence of food they persist in a stress resistant, developmentally arrested state (L1 arrest). We characterized mRNA expression genome-wide in a pair of bifurcating time series starting in the late embryo and proceeding through the hatch in the presence and absence of food (E. coli).
Publication Title
RNA Pol II accumulates at promoters of growth genes during developmental arrest.
Sample Metadata Fields
No sample metadata fields
View Samples