Filters
Technology
Platform
Mus musculus
8 Downloadable Samples
NextSeq 500
Description
KRAS mutation is present in about 30% of human lung adenocarcinomas. While recent advances in targeted therapy have shown great promise, KRAS remains undruggable and concurrent alterations in tumor suppressors render KRAS mutant tumors even more resistant to existing therapies. Contributing to the refractoriness of KRAS mutant tumors harboring these co-mutations are immunosuppressive mechanisms such as increased presence of suppressive Tregs in tumors and elevated expression of the inhibitory receptor PD-1 on tumor-infiltrating T cells. BET bromodomain inhibitors demonstrate clinical benefit in hematologic malignancies, and prior reports demonstrate their Treg-disruptive effects in a NSCLC model. Targeting PD-1 inhibitory signals through anti-PD-1 antibody blockade has also shown substantial therapeutic impact in lung cancer although these outcomes are still limited to a minor pool of patients. We therefore hypothesized that the BET bromodomain inhibitor JQ1 would synergize with PD-1 blockade to promote robust anti-tumor response in lung cancer. In the present study, using Kras+/LSL-G12D; Trp53L/L (KP) mouse models of non-small cell lung cancer, we identified cooperative effects between JQ1 and anti-PD-1 antibody that included reduced numbers of tumor-infiltrating Tregs and enhanced activation of tumor-infiltrating T cells, which exhibited a Th1 cytokine profile that favored their demonstrated improved effector function. Furthermore, lung-tumor-bearing mice under this combinatorial treatment regimen showed robust and long-lasting anti-tumor responses compared to either agent alone, culminating in substantial improvement in the survival of treated mice. Thus, combining BET bromodomain inhibition with immune checkpoint blockade offers a promising therapeutic approach for solid malignancies such as lung adenocarcinoma. Overall design: Gene expression analyses of tumor nodules in lung tumor-bearing mice treated with Vehicle (control), JQ1 (Bromodomain inhibitor) and/or anti-PD-1 antibody
Publication Title
BET Bromodomain Inhibition Cooperates with PD-1 Blockade to Facilitate Antitumor Response in <i>Kras</i>-Mutant Non-Small Cell Lung Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 33 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 33 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of mRNA samples purified from developing cerebellar granule cells and ES cell-derived granule cells using translating ribosome affinity purification (TRAP) method.
Publication Title
Role of Tet1/3 Genes and Chromatin Remodeling Genes in Cerebellar Circuit Formation.
Sample Metadata Fields
Specimen part
View Samples
GSE1825- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of gene expression profiles between neuroblastoma samples and Ewing family tumor samples. RNA from native tumor samples was processed for DNA-microarray analysis using Affymetrix HG-U133A microarrays. Primary image analysis was performed using MAS 5.0 and data were scaled to an target intesity of 500.
Publication Title
DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets.
Sample Metadata Fields
No sample metadata fields
View Samples GSE1824- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Gene expression analysis of cell lines initially established as neuroblastoma cell lines. Cells were harvested and processed for DNA-microarray analysis using Affymetrix HG-U133A microarrays. Primary image analysis was performed using MAS 5.0 and data were scaled to an target intesity of 500.
Publication Title
DNA microarrays reveal relationship of Ewing family tumors to both endothelial and fetal neural crest-derived cells and define novel targets.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 27 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 27 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Eco1 is an acetyltransferase subunit of the cohesin complex and acts during DNA replication to establish cohesion between sister chromatids. However, cohesin has additional functions in gene expression, DNA damage repair, and higher-order organization of chromosomes. The eco1 mutant W216G disrupts acetyltansferase activity, and causes genome-wide transcriptional defects which can be suppressed by deletion of FOB1, a gene also involved in DNA replication. This experiment investigates gene expression differences between the eco1-W216G mutant, and mutants in FOB1, and RAD61 a gene involved in inhibition of cohesion establishment but mutation of which is able to suppress temperature sensitivity of the eco1-W216G mutant.
Publication Title
The cohesin acetyltransferase Eco1 coordinates rDNA replication and transcription.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
Publication Title
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To model human cerebellar disease, we developed a novel, reproducible method to generate cerebellar Purkinje cells (PCs) from human pluripotent stem cells (hPSCs) that formed synapses when cultured with mouse granule cells and fired large calcium currents, measured with the genetically encoded calcium indicator jRGECO1a. Using translating ribosomal affinity purification (TRAP) to compare gene expression of differentiating hPSC-PCs to developing mouse PCs, we found hPSC-PCs to be most similar to late juvenile (P21) mouse PCs. Analysis of mouse PCs defined novel developmental expression patterns for mitochondria and autophagy associated genes, recapitulated in hPSC-PCs. We further identified species differences in gene expression and confirmed protein expression of CD40LG in native human, but not mouse PCs. This study provides a robust method for generating relatively mature hPSC-PCs with human specific gene expression and defines novel genetic features in comparison to the first comprehensive analysis of global gene expression patterns of postnatal mouse PC development.
Publication Title
Novel genetic features of human and mouse Purkinje cell differentiation defined by comparative transcriptomics.
Sample Metadata Fields
No sample metadata fields
View Samples