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Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD4+ T cell help is critical for optimal CD8+ T cell expansion after priming in many experimental systems. However, a role for CD4+ T cells in regulating the initial steps of CD8+ T cell effector differentiation is not well established. Here we demonstrate that absence of CD4+ T cells at the time of replication-incompetent adenovirus vector immunization of C57BL/6 mice led to immediate CD8+ T cell dysfunction characteristic of exhaustion at the first detectable timepoints as well as impaired expansion of antigen-specific CD8+ T cells. The absence of CD4+ T cell help resulted in antigen-specific CD8+ T cells that had reduced ex vivo cytotoxicity and decreased capacity to produce IFN- and TNF-. CD8+ T cells primed in the absence of CD4+ T cells expressed elevated levels of the inhibitory receptors PD-1, LAG-3, and Tim-3, and these cells exhibited transcriptomic exhaustion profiles by gene set enrichment analysis. This dysfunctional state was imprinted within 3 days of immunization and could not be reversed by provision of CD4+ T cell help after priming. Partial rescue of unhelped CD8+ T cell expansion and effector differentiation could be achieved by PD-1 pathway blockade or recombinant IL-2 administration.
Publication Title
Immediate Dysfunction of Vaccine-Elicited CD8+ T Cells Primed in the Absence of CD4+ T Cells.
Sample Metadata Fields
Specimen part, Time
View Samples- Macaca mulatta
- 46 Downloadable Samples
- Rhesus Gene 1.0 ST Array (rhegene10st)
Description
Zika virus (ZIKV) is responsible for a major current outbreak in the Americas and has been causally associated with fetal microcephaly as well as Guillain-Barre syndrome in adults. However, the immune responses associated with controlling ZIKV replication remain poorly characterized. Here we report a detailed analysis of innate and adaptive immune responses following ZIKV infection in 16 rhesus monkeys. A robust proinflammatory innate immune response was observed within the first few days of infection, including upregulation of type 1 interferon, which correlated directly with viral loads. Immunomodulatory pathways, including IL-10 and TGF-, were also upregulated. ZIKV-specific neutralizing antibodies emerged rapidly by day 7 and correlated inversely with viral loads, which were undetectable in peripheral blood by day 6-10. In contrast, virus replication persisted in cerebrospinal fluid (CSF) for at least 21-42 days in 75% (3 of 4) of the monkeys that received the lowest dose of ZIKV tested, and ZIKV-specific antibodies were essentially undetectable in CSF. These data suggest that antibodies play a critical role in the rapid control of acute viremia in the periphery but were largely excluded from the central nervous system, allowing viral persistence at this immuonoprivileged site.
Publication Title
Zika Virus Persistence in the Central Nervous System and Lymph Nodes of Rhesus Monkeys.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Using stem cellbased therapies to treat retinal abnormalities is becoming a likely possibility; therefore, identifying the key factors and the relevant mechanisms controlling optic vesicle morphogenesis and neuroretina (NR) differentiation is important. Recent advances in self-organizing, 3-dimensional (3D) tissue cultures of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) provided a valuable in vitro model for characterizing regulatory cascades and signaling pathways controlling mammalian retinal development. Using Rx-GFP expressing ESCs and Six3/ iPSCs we identified R-spondin 2 (Rspo2)-mediated repression of Wnt signaling as a novel required step during optic vesicle morphogenesis and NR differentiation. Furthermore, we also show that transient ectopic expression of Rspo2 in the anterior neural plate of transgenic mouse embryos was sufficient to arrest NR differentiation. ChIP assays identified Six3-responsive elements in the Rspo2-promoter region, indicating that Six3-mediated repression of Rspo2 is required to restrict Wnt signaling in the developing anterior neuroectoderm and allow eye development to proceed.
Publication Title
An Eye Organoid Approach Identifies Six3 Suppression of R-spondin 2 as a Critical Step in Mouse Neuroretina Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND:
Publication Title
Clinical, radiographic, and biochemical characterization of multiple myeloma patients with osteonecrosis of the jaw.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 18 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Intralocus sexual conflict, where males and females have different fitness optima for the same trait, has been suggested to potentially be resolved by genomic imprinting, whereby expression in offspring is altered according to parent-of-origin. However, this idea has not yet been empirically tested. Here, we designed an experimental evolution protocol in Drosophila melanogaster which enabled us to look for imprinting effects on the X-chromosome. We enforced father-to-son transmission of the X-chromosome for many generations, and compared fitness and gene expression levels between control males, males with a control X-chromosome that had undergone one generation of father-son transmission (CDX), and males with an X-chromosome that had undergone many generations of father-son transmission (MLX). Although fitness differences were consistent with lowered fitness of males with a paternally inherited X-chromosome, expression differences suggested that this was due to deleterious maternal effects rather than imprinting. We conclude that imprinting is unlikely to resolve intralocus sexual conflict in Drosophila melanogaster.
Publication Title
Epigenetics and sex-specific fitness: an experimental test using male-limited evolution in Drosophila melanogaster.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The Rac nucleotide Exchange Factor (Rac-GEF) P-Rex1 is highly expressed in breast cancer, specifically in the luminal subtype, and is an essential mediator of actin cytoskeleton reorganization and cell migratory responses induced by ErbB and other tyrosine-kinase receptors. Heregulin, a growth factor highly expressed in mammary tumors, causes the activation of P-Rex1 and Rac1 in breast cancer cells via ErbB3, leading to a motile response. Since there is limited information about P-Rex1 downstream effectors, we carried out a microarray analysis to identify genes regulated by P-Rex1 in the context of HRG stimulation. In T-47D breast cancer cells, HRG treatment caused major changes in gene expression, including genes associated with motility, adhesion, invasiveness and metastasis. Silencing P-Rex1 expression from T-47D cells using RNAi altered the induction and repression of a subset of HRG-regulated genes, among them genes associated with extracellular matrix organization, migration, and chemotaxis. HRG induction of MMP10, a gene encoding for metalloproteinase-10, was found to be highly sensitive both to P-Rex1 depletion as well as inhibition of Rac1 function by the GTPase Activating Protein (GAP) 2-chimaerin, suggesting the dependence of the P-Rex1/Rac1 pathway for the induction of genes critical for breast cancer invasiveness. Notably, there is a significant association in the expression of P-Rex1 and MMP10 in human luminal breast cancer, and their co-expression is indicative of poor prognosis.
Publication Title
Characterization of a P-Rex1 gene signature in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
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GSE11057- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples.
Publication Title
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Sample Metadata Fields
Specimen part, Disease
View Samples GSE11058- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. Its ability to discriminate related human cells is unknown.
Publication Title
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by increased ovarian androgen production, arrested follicle development, and is frequently associated with insulin resistance. These PCOS phenotypes are associated with exaggerated ovarian responsiveness to FSH and increased pregnancy loss. To examine whether the perturbations in follicle growth and the intrafollicular environment affects development of the mature PCOS oocyte, genes that are differentially expressed in PCOS compared to normal oocytes were defined using microarray analysis. This analysis detected approximately 8000 transcripts. Hierarchical clustering and principal component analysis revealed differences in global gene expression profiles between normal and PCOS oocytes. 374 genes had a statistically-significant increase or decrease in mRNA abundance in PCOS oocytes. A subset of these genes was associated with chromosome alignment and segregation during mitosis and/or meiosis, suggesting that increased mRNAs for these proteins may negatively affect oocyte maturation and/or early embryonic development. Of the 374 differentially expressed genes, 68 contained putative androgen receptor, retinoic acid receptor, and/or peroxisome proliferating receptor gamma binding sites, including 9 of the genes involved in chromosome alignment and segregation. These analyses demonstrated that normal and PCOS oocytes that are morphologically indistinguishable and of high quality exhibit different gene expression profiles. Furthermore, altered mRNA levels in the PCOS oocyte may contribute to defects in meiosis and/or mitosis which might impair oocyte competence for early development and therefore contribute to poor pregnancy outcome in PCOS.
Publication Title
Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis.
Sample Metadata Fields
No sample metadata fields
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