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GSE149425
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The PD-1:PD-L co-inhibitory pathway regulates dysfunctional T cells in chronic viral infection and cancer, but the role of this pathway in effector and memory responses following acute infection or vaccination remains less clear. Here we demonstrated that in the absence of signals from the PD-1 pathway, cell intrinsic alterations during initial CD8+ T cell priming resulted in excessive early CD8+ T cell expansion, but increased CD8+ T cell contraction and aberrant effector to memory CD8+ T cell transition. Overall, our studies revealed a critical and previously unappreciated role for PD-1 as an integrator of early CD8+ T cell activation signals that promoted optimal CD8+ T cell memory formation and durability. This novel PD-1 function has therapeutic implications for the generation of T cell memory during PD-1 cancer immunotherapy and modulation of the PD-1 pathway to enhance immune memory following acute infection or prophylactic vaccination.
Publication Title
The PD-1 Pathway Regulates Development and Function of Memory CD8<sup>+</sup> T Cells following Respiratory Viral Infection.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Exhausted T cells express multiple co-inhibitory molecules that impair their function and limit immunity to chronic viral infection. Defining novel markers of exhaustion is important both for identifying and potentially reversing T cell exhaustion. Herein, we show that the ectonucleotidse CD39 is a marker of exhausted CD8+ T cells. CD8+ T cells specific for HCV or HIV express high levels of CD39, but those specific for EBV and CMV do not. CD39 expressed by CD8+ T cells in chronic infection is enzymatically active, co-expressed with PD-1, marks cells with a transcriptional signature of T cell exhaustion and correlates with viral load in HIV and HCV. In the mouse model of chronic Lymphocytic Choriomeningitis Virus infection, virus-specific CD8+ T cells contain a population of CD39high CD8+ T cells that is absent in functional memory cells elicited by acute infection. This CD39high CD8+ T cell population is enriched for cells with the phenotypic and functional profile of terminal exhaustion. These findings provide a new marker of T cell exhaustion, and implicate the purinergic pathway in the regulation of T cell exhaustion.
Publication Title
CD39 Expression Identifies Terminally Exhausted CD8+ T Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
Illumina HiSeq 2000
Description
The goal of this study is to investigate if interferon signaling regulates immune checkpoint blockade in mouse melanoma model. Overall design: Transcription profiling for B16, B16 after chronic interferon treatment, B16 derived checkpoint blockade resistant strain 499 and various knockout from 499, coupled with ATA-seq data.
Publication Title
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Response to immune checkpoint inhibitors may be improved through combinations with each other and other therapies, raising questions about non-redundancy and resistance. We report results from parallel studies of melanoma patients and mice treated with anti-CTLA4 and radiation (RT). Although combined treatment improved responses, resistance was common. Computational analyses of immune and transcriptomic profiles (provided here) revealed that resistance in mice was due to upregulation of tumor PD-L1 that drives T cell exhaustion. Accordingly, optimal response requires RT, anti-CTLA4, and anti-PD-L1. Anti-CTLA4 inhibits Tregs, RT diversifies and shapes the TCR repertoire, and anti-PD-L1 reinvigorates exhausted T cells. Together, all three therapies promote the expansion of clonotypes with distinct TCR traits. Similar to mice, patients with melanoma showing high PD-L1 did not respond to RT + anti-CTLA4, demonstrated persistent T cell exhaustion, and rapidly progressed. Thus, the combination of RT, anti-CTLA4, and anti-PD-L1 promotes response through distinct mechanisms.
Publication Title
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Male fertility and testis function changes with age and so it was sought to determine if these changes are accompanied by changes in gene expression.
Publication Title
Aging results in differential regulation of DNA repair pathways in pachytene spermatocytes in the Brown Norway rat.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- NextSeq 500
Description
The root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays. Single root tip zones can be used for full transcriptome analysis; further, the root apex zones are functionally very distinct from each other. RNA-Seq provided novel information about the transcripts compared to the arrays. These data will help optimize transcriptome techniques for dealing with small, rare samples. Overall design: Arabidopsis thaliana var. Columbia (COL-0) seedlings were grown on sterile solid media plates containing 0.5 % phytagel. The plates were vertically placed in growth chambers with continuous light (80-100 µmol m -2) at a constant temperature of 19° C. Eight day old seedlings were harvested into RNA-later solution in a 50 mL centrifuge tubes and stored at -20 °C freezer. The root tips were dissected into zone-I: 0.5mm from the tip including the root cap and root division zones, and zone-II: 1.5mm sections including root elongation and root hair zone. Microarray and sequencing experiments were performed.
Publication Title
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Caenorhabditis elegans
- 14 Downloadable Samples
- Illumina HiSeq 2000
Description
Stressors may have negative or positive effects in dependence of the dose (hormesis). We studied this phenomenon in Caenorhabditis elegans by applying weak or severe abiotic (cadmium, CdCl2) and/or biotic stress (different bacterial diets) during cultivation/breeding of the worms, and determining developmental speed or survival rates and performing transcriptome profiling and RT-qPCR analyses to explore the genetic basis of the detected phenotypic differences. This study showed that a bacterial diet resulting in higher levels of energy resources in the worms (E. coli OP50 feeding) or weak abiotic and biotic stress especially promote the resistance against severe abiotic or biotic stress and the age-specific survival rate of WT. Overall design: Five experimental conditions; mostly three replicates per experimental condition; four contrasts between test and control conditions functionally analyzed.
Publication Title
Bacterial diet and weak cadmium stress affect the survivability of <i>Caenorhabditis elegans</i> and its resistance to severe stress.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Sample Metadata Fields
Age, Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The root apex is an important section of the plant root, involved in environmental sensing and cellular development. Analyzing the gene profile of root apex in diverse environments is important and challenging, especially when the samples are limiting and precious, such as in spaceflight. The feasibility of using tiny root sections for transcriptome analysis was examined in this study.To understand the gene expression profiles of the root apex, Arabidopsis thaliana Col-0 roots were sectioned into Zone-I (0.5 mm, root cap and meristematic zone) and Zone-II (1.5 mm, transition, elongation and growth terminating zone). Gene expression was analyzed using microarray and RNA seq.Both the techniques, arrays and RNA-Seq identified 4180 common genes as differentially expressed (with > two-fold changes) between the zones. In addition, 771 unique genes and 19 novel TARs were identified by RNA-Seq as differentially expressed which were not detected in the arrays.
Publication Title
Comparing RNA-Seq and microarray gene expression data in two zones of the <i>Arabidopsis</i> root apex relevant to spaceflight.
Sample Metadata Fields
Age, Specimen part
View Samples- Schizosaccharomyces pombe
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Spc1/ Spc1K49R was overexpressed in wt S. pombe cells for 24 hours and gene expression changes were analysed
Publication Title
Genome wide transcription profiling of the effects of overexpression of Spc1 and its kinase dead mutant in Schizosaccharomyces pombe.
Sample Metadata Fields
No sample metadata fields
View Samples