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GSE43929
Mus musculus
4 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
To understand why cancer vaccine-induced T cells often fail to eradicate tumors, we studied immune responses in mice vaccinated with gp100 peptide emulsified in incomplete Freund's adjuvant (IFA), commonly used in clinical cancer vaccine trials. After gp100 peptide/IFA vaccination, tumor-specific CD8+ T cells (adoptively transferred from gp100-specific TCR-transgenic pmel-1 mice) accumulated not in tumors but at the persisting, antigen-rich vaccination site. Once there, primed T cells became dysfunctional and underwent antigen-driven, IFN- and FasL-mediated apoptosis, resulting in systemic hyporesponsiveness to subsequent vaccination. Provision of anti-CD40 antibody, TLR7 agonist and interleukin-2 (covax) reduced T cell apoptosis but did not prevent vaccination site sequestration. A non-persisting vaccine formulation shifted T cell localization towards tumors, inducing superior anti-tumor activity. Short-lived formulation also reduced systemic T cell dysfunction and promoted memory formation, as shown by gene expression profiling and other measures. Persisting peptide/IFA vaccine depots, currently used to vaccinate cancer patients, can induce specific T cell sequestration at vaccination sites followed by dysfunction and deletion; short-lived depot formulations may overcome these limitations and result in greater therapeutic efficacy of peptide-based cancer vaccines.
Publication Title
Persistent antigen at vaccination sites induces tumor-specific CD8⁺ T cell sequestration, dysfunction and deletion.
Sample Metadata Fields
Specimen part, Time
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used yeast RNA to estimate background binding for each probe on the human U133 plus 2.0 array.
Publication Title
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Sample Metadata Fields
Treatment
View Samples- Saccharomyces cerevisiae
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We hybridized yeast RNA to the mouse 430 2.0 array to estimate the background binding for each probe.
Publication Title
The Gene Expression Barcode: leveraging public data repositories to begin cataloging the human and murine transcriptomes.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Identification of novel differentially expressed genes in human M1 and M2 macrophages using RNA-Seq Overall design: RNA-Seq was performed using RNA from M1 and M2-polarized macrophages from 4 biological replicates
Publication Title
Transcriptional profiling identifies novel regulators of macrophage polarization.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Estrogen plays an important role in the regulation of vascular tone and in the pathophysiology of cardiovascular disease. Physiological effects of estrogen are mediated through estrogen receptors alpha (ERalpha) and beta (ERbeta), which are both expressed in vascular smooth muscle and endothelial cells. However, the molecular pathways mediating estrogen effects in blood vessels are not well defined. We have performed gene expression profiling in the mouse aorta to identify comprehensive gene sets the expression of which is regulated by long-term (1 wk) estrogen treatment. The ER subtype dependence of the alterations in gene expression was characterized by parallel gene expression profiling experiments in ERalpha-deficient [ERalpha knockout (ERalphaKO)] and ERbeta-deficient (ERbetaKO) mice.
Publication Title
Estrogen receptors alpha and beta mediate distinct pathways of vascular gene expression, including genes involved in mitochondrial electron transport and generation of reactive oxygen species.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The steroid hormone aldosterone plays a role in vascular function and disease. Aldosterone activates the mineralocorticoid receptor (MR), a ligand-activated transcription factor. MR have been found to be expressed in vascular cells and vessels.
Publication Title
Placental growth factor mediates aldosterone-dependent vascular injury in mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used a smooth muscle cell-specific mineralocorticoid receptor knockout mouse to generate young and aged MR-intact and SMC-MR-KO aortic mRNA to examine the effect of age on vascular mRNA alterations in the presence and absence of SMC-MR.
Publication Title
Smooth Muscle Cell-Mineralocorticoid Receptor as a Mediator of Cardiovascular Stiffness With Aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Histone variant H2A.Z occupies the promoters of active and poised, bivalent genes in ESCs to regulate developmental programs, yet how it contributes to these contrasting states is poorly understood. Here, we investigate the function of H2A.Z.1 mono-ubiquitylation (H2A.Z.1ub) by mutation of the PRC1 target residues (H2A.Z.1K3R3). We show that H2A.Z.1K3R3 is properly incorporated at target promoters in murine ESCs (mESCs), however, loss of mono-ubiquitylation leads to de-repression of bivalent genes, loss of Polycomb binding, and to faulty lineage commitment. Using quantitative proteomics, we find that tandem bromodomain proteins, including the BET family member Brd2, are enriched in H2A.Z.1 chromatin. We further show that Brd2 is gained at de-repressed promoters in H2A.Z.1K3R3 mESCs whereas Brd2 inhibition restores gene silencing at these sites. Together, our study reveals an antagonistic relationship between H2A.Z.1ub and Brd2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs. Overall design: RNA-Seq analysis on mouse embryonic stem cells harboring H2A.Z or H2A.Z.K3R3 (3 C-terminal lysines mutated to arginines) tagged with YFP, in the presence of a knockdown hairpin targeting the endogenous H2A.Z transcript.
Publication Title
H2A.Z.1 Monoubiquitylation Antagonizes BRD2 to Maintain Poised Chromatin in ESCs.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- IlluminaHiSeq2500
Description
Polycomb Repressive Complex 2 (PRC2) plays crucial roles in transcriptional regulation and stem cell development. However, the context-specific functions associated with alternative subunits remain largely unexplored. Here we show that the related enzymatic subunits EZH1 and EZH2 undergo an expression switch during hematopoiesis. We examine the in vivo stoichiometry of the PRC2 complexes by quantitative proteomics and reveal the existence of an EZH1-SUZ12 sub-complex lacking EED. We provide evidence that EZH1 together with SUZ12 form a non-canonical PRC2 complex, occupy active chromatin domains in the absence of H3K27me3, and positively regulate gene expression. Loss of EZH2 expression leads to global repositioning of EZH1 chromatin occupancy to EZH2 targets. Moreover, we demonstrate that an erythroid-specific enhancer mediates transcriptional activation of EZH1, and a switch from GATA2 to GATA1 controls the developmental EZH1/2 switch by differential association with EZH1 enhancers during erythropoiesis. Thus, the lineage- and developmental stage-specific regulation of PRC2 expression and subunit composition leads to a switch from canonical silencing to non-canonical PRC2 functions during blood stem cell specification. Overall design: Transcriptional profiling in primary human fetal liver proerythroblasts upon lentiviral shRNA-mediated knockdown of EZH1, EZH2, EED, or SUZ12 by RNA-seq analysis.
Publication Title
Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions.
Sample Metadata Fields
No sample metadata fields
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