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GSE143007
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- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The mRNA processing body is a cellular structure that regulates the stability of cytoplasmic mRNA. MARF1/LMKB is an RNA-binding protein that is associated with maintenance of mRNA homeostasis and genomic stability. To investigate the function of LMKB in a human B lymphocyte cell line, BJAB cells were treated with either control lentivirus or a lentivirus containing LMKB siRNA.
Publication Title
LMKB/MARF1 localizes to mRNA processing bodies, interacts with Ge-1, and regulates IFI44L gene expression.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Prostate cancer is the most commonly diagnosed malignancy in the United States. While the majority of cases are cured with radiation or surgery, about 1/3 of patients will develop metastatic disease which there is no cure, and has a life expectancy of less than 5 years. Identification of antigens associated with this transition to metastatic disease is crucial for future therapies. One such antigen of interest is the SSX gene family, which are cancer/testis antigens that are associated with the epithelial to mesenchymal transition in other cancer types. Prior work has shown that, in prostate cancer, SSX expression was restricted to metastatic tissue and not primary tumor tissue which may indicate a role in disease progression. Some work has been done into the function of the SSX family, which revealed transcriptional regulator activity. But neither the targets of this activity or the function of SSX are known. Through a transcriptomics approach, we are seeking a better understanding of the different genes and pathways SSX regulates in the context of prostate cancer, and to determine if these pathways may contribute to disease progression.
Publication Title
SSX2 regulates focal adhesion but does not drive the epithelial to mesenchymal transition in prostate cancer.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Primary human hepatocytes (PHH) are a main instrument in drug metabolism research and in the prediction of drug-induced phase I/II enzyme induction in humans. The HepG2 liver-derived cell line is commonly used as a surrogate for human hepatocytes, but their use in ADME and toxicity studies can be limited because of lowered basal levels of metabolizing enzymes. Despite their widespread use, the transcriptome of HepG2 cells compared to PHH is not well characterized. In this study, microarray analysis was conducted to ascertain the differences and similarities in mRNA expression between HepG2 cells and human hepatocytes before and after exposure to a panel of fluoroquinolone compounds. Comparison of the nave HepG2 cell and PHH transcriptomes revealed a substantial number of basal gene expression differences. When HepG2 cells were dosed with a series of fluoroquinolones, trovafloxacin, which has been associated with human idiosyncratic hepatotoxicity, induced substantially more gene expression changes than the other quinolones, similar to previous observations with PHH. While TVX-treatment resulted in many gene expression differences between HepG2 cells and PHH, there were also a number of TVX-induced commonalities, including genes involved in RNA processing and mitochondrial function. Taken together, these results provide insight for interpretation of results from drug metabolism and toxicity studies conducted with HepG2 cells in lieu of PHH, and could provide further insight into the mechanistic evaluation of TVX-induced hepatotoxicity.
Publication Title
Trovafloxacin-induced gene expression changes in liver-derived in vitro systems: comparison of primary human hepatocytes to HepG2 cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 18 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In this study we have examined the effect of sub-cytotoxic exposure to aristolochic acids (1.65M) at 6h, 24h and 72h on the whole-genome expression profile in a rat proximal renal tubule cell line (NRK-52E).
Publication Title
Aristolochic acids - Induced transcriptomic responses in rat renal proximal tubule cells in vitro.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 5 Downloadable Samples
Illumina HiSeq 2500
Description
Viral infection can dramatically alter a cell''s transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in production of viral gene transcripts -- viral transcripts compose less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, and this gene absence partially explains variation in viral transcriptional load. Despite variation in total viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells. Overall design: Dataset consists of a total of five single-cell datasets generated using the 10x Genomics Chromium Single Cell 3'' Solution platform. All samples were generated from a tissue culture infection model using A549 cells from ATCC and Influenza A/WSN/1933 virus. Uninfected control sample identically processed. Infected samples were generated from cells infected for 6, 8, and 10 hours with a single replicate at 8 hours.
Publication Title
Extreme heterogeneity of influenza virus infection in single cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 56 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
To acquire a better understanding of the molecular pathogenesis of HS, we performed mRNA microarray studies to compare gene expression in lesional skin to healthy skin of HS patients.
Publication Title
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
To acquire a better understanding of the molecular pathogenesis of hidradenitis suppurativa (HS), we performed mRNA microarray studies to compare whole blood gene expression of HS patients to that of healthy normal subjects.
Publication Title
Gene expression profiling of skin and blood in hidradenitis suppurativa.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Individuals expressing alpha-1-antitrypsin mutant Z protein accumulate misfolded, mutant protein in the liver and are at risk for liver diseases including cirrhosis and hepatocellular carcinoma. Transgenic PiZ mice, a model for this liver disease, display similar pathologies to humans, including inflammation, increases in proliferation, autophagy and apoptosis, accumulation of globules and develop fibrosis and hepatocellular carcinoma with age. Microarrays were used to compare the gene expressions of PiZ mice to wild-type mice in order to identify the pathways that are altered in this disorder.
Publication Title
Oxidative stress contributes to liver damage in a murine model of alpha-1-antitrypsin deficiency.
Sample Metadata Fields
Sex, Specimen part
View Samples