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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
- 770 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
We analyzed samples from 770 male human subjects who are part of the METSIM study. Ethics Committee of the Northern Savo Hospital District approved the study. All participants gave written informed consent. The population-based cross-sectional METSIM study included 10 197 men, aged from 45 to 73 years, who were randomly selected from the population register of the Kuopio town in eastern Finland (population 95000). Every participant had a 1-day outpatient visit to the Clinical Research Unit at the University of Kuopio, including an interview on the history of previous diseases and current drug treatment and an evaluation of glucose tolerance and cardiovascular risk factors. After 12 h of fasting, a 2 h oral 75 g glucose tolerance test was performed and the blood samples were drawn at 0, 30 and 120 min. Plasma glucose was measured by enzymatic hexokinase photometric assay (Konelab Systems reagents; Thermo Fischer Scientific, Vantaa, Finland). Insulin was determined by immunoassay (ADVIA Centaur Insulin IRI no. 02230141; Siemens Medical Solutions Diagnostics, Tarrytown, NY, USA). Height and weight were measured to the nearest 0.5 cm and 0.1 kg, respectively. Waist circumference (at the midpoint between the lateral iliac crest and lowest rib) and hip circumference (at the level of the trochanter major) were measured to the nearest 0.5 cm. Body composition was determined by bioelectrical impedance (RJL Systems) in subjects in the supine position.
Publication Title
Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Bile acids are not only physiological detergents facilitating nutrient absorption, but also signaling molecules regulating metabolic homeostasis. We reported recently that transgenic expression of CYP7A1 in mice stimulated bile acid synthesis and prevented Western diet-induced obesity, insulin resistance and hepatic steatosis. The aim of this experiment is to determine the impact of induction of hepatic bile acid synthesis on liver metabolism by determining hepatic gene expression profile in CYP7A1 transgenic mice. CYP7A1 transgenic mice and wild type control mice were fed either standard chow diet or high fat high cholesterol Western diet for 4 month. Hepatic gene expressions were measured by microarray analysis. Our results indicate that hepatic bile acid synthesis is closely linked to cholesterogenesis and lipogenesis, and maintaining bile acid homeostasis is improtant in hepatic metabolic homeostasis.
Publication Title
Regulation of cholesterol and bile acid homeostasis by the cholesterol 7α-hydroxylase/steroid response element-binding protein 2/microRNA-33a axis in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Caenorhabditis elegans
- 5 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Genome-wide expression analysis in C. Elegans grown in axenic media with low to toxic selenium concentrations
Publication Title
Toxic-selenium and low-selenium transcriptomes in Caenorhabditis elegans: toxic selenium up-regulates oxidoreductase and down-regulates cuticle-associated genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Natural killer (NKT) T cells exhibit tissue distribution, surface phenotype, and functional responses that are strikingly different from those of conventional T cells. The transcription factor PLZF is responsible for most of these properties, as its ectopic expression in conventional T cells is sufficient to confer to them an NKT-like phenotype. The molecular program downstream of PLZF, however, is largely unexplored.
Publication Title
PLZF Controls the Expression of a Limited Number of Genes Essential for NKT Cell Function.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
IonTorrentProton
Description
Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment. Overall design: Vehicle control, diclofenac, and three doses of the test compound (small-molecule neurotransmitter receptor antagonist) were applied to three primary cell lines, with three biological replicates in each group. In some treatment groups read-outs were only available for two samples. All together 41 samples were profiled.
Publication Title
Pathway reporter genes define molecular phenotypes of human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We have determined the consequences of ICN1 overexpression from retroviral vectors introduced into bone marrow cells.
Publication Title
Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of stemness genes. The present study describes the construction and comparative molecular analysis of l-phage cDNA libraries from highly purified primitive HSCs (PHSCs) which retained their long term repopulating activities (LTRAs), and from maturing HSCs (MHSCs) which were largely depleted of LTRAs. Library inserts were amplified and tagged by a T7 RNA polymerase promoter and used to generate biotinylated cRNA for Microarray hybridization. Microarray analysis of the libraries confirmed previous results but also revealed an unforseen preferential expression of translation and metabolism associated genes in the PHSCs. Therefore these data indicate that HSCs are quiescent only in regard of proliferative activities, but are in a state of readiness to provide the metabolic and translational activities required following induction of proliferation by factors which induce differentiation and exit from the HSC pool.
Publication Title
Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) and dark zone (DZ) germinal center (GC) B cells were compared in immunized AIDcre/- IgH-96K/+ R26-LSL-YFP mice.
Publication Title
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) germinal center (GC) B cells that were Nurr77-GFP+ or Nurr77-GFP- were compared in immunized AIDcre/- IgH-96K/+ Nurr77-GFP mice.
Publication Title
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples