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GSE65627
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The optimal T cell attributes for the adoptive immunotherapy of cancer and viral diseases are currently unclear. Recent adoptive transfer clinical trials using ex vivo expanded tumor infiltrating lymphocytes has provided evidence that differentiated effector T cells can mediate durable responses in selected cancer patients. The capacity of these transferred cells to persist in the host was found to strongly correlate with their clinical activity. Thus, there is significant interest in identifying intrinsic markers that define antigen specific effector T cells that can develop into long-lived memory cells rather than undergoing apoptosis after infusion in humans. We recently reported the long term persistence of ex vivo expanded tumor specific CD8+ T effector clones in refractory metastatic melanoma patients after adoptive T cell transfer. By utilizing these highly homogeneous clone populations, we sought to define the pre-infusion cellular and molecular attributes associated with their effector to memory transition. Comparative transcriptional profiling found the pre-infusion clone mRNA expression levels of the IL-7 receptor (IL-7Ra) and the proto-oncogene, c-myc, directly correlated with the level of clonal persistence after adoptive transfer in humans. The predictive value of these markers was further established by utilizing IL-7R protein, induced pSTAT5, and c-myc mRNA expression to prospectively identify human tumor specific effector clones that could engraft after controlled adoptive transfer into highly immunodeficient mice. These findings support that IL-7R and c-myc expression are valuable cell intrinsic markers that can predict the fate of effector CD8+ T cells after adoptive transfer.
Publication Title
Tumor-Specific Effector CD8+ T Cells That Can Establish Immunological Memory in Humans after Adoptive Transfer Are Marked by Expression of IL7 Receptor and c-myc.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Introduction: A major challenge in the interpretation of genomic profiling data generated from breast cancer samples is the identification of driver genes as distinct from bystander genes which do not impact tumorigenesis. One way to assess the relative importance of alterations in the transcriptome profile is to combine complementary analyses that assess changes in the copy number alterations (CNAs). This integrated analysis permits the identification of genes with altered expression that map within specific chromosomal regions that demonstrate copy number alterations, providing a mechanistic approach to identify the 'driver genes.
Publication Title
Integration of transcript expression, copy number and LOH analysis of infiltrating ductal carcinoma of the breast.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Transcriptome analysis of LDBM cells stimulated with IL-5
Publication Title
IL-5 triggers a cooperative cytokine network that promotes eosinophil precursor maturation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
Illumina Genome Analyzer II
Description
T cell development comprises a stepwise process of commitment from a multipotent precursor. To define molecular mechanisms controlling this progression, we probed five stages spanning the commitment process using deep sequencing RNA-seq and ChIP-seq methods to track genome-wide shifts in transcription, cohorts of active transcription factor genes, histone modifications at diverse classes of cis-regulatory elements, and binding patterns of GATA-3 and PU.1, transcription factors with complementary roles in T-cell development. The results locate potential promoter-distal cis-elements in play and reveal both activation sites and diverse mechanisms of repression that silence genes used in alternative lineages. Histone marking is dynamic and reversible, and while permissive marks anticipate, repressive marks often lag behind changes in transcription. In vivo binding of PU.1 and GATA-3 relative to epigenetic marking reveals distinctive, factor-specific rules for recruitment of these crucial transcription factors to different subsets of their potential sites, dependent on dose and developmental context. Overall design: Genome-wide expression profiles, global distributions of three different histone modifications, and global occupancies of two transcription factors were examined in five developmentally related immature T populations. High throughput sequencing generated on average 9-30 million of mappable reads (single-read) for each ChIP-seq sample, and 10-15 million (single-read) for RNA-seq. Independent biological replicates were analyzed for individual populations. Terminology: FLDN1_RNA-seq_sample1 and FLDN1_RNA-seq_sample2 are independent biological replicates for the same cell type.
Publication Title
Dynamic transformations of genome-wide epigenetic marking and transcriptional control establish T cell identity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Human B-1 cells (CD20+CD27+CD43+CD38lo/int) and pre-plasmablast like cells (CD20+CD27hiCD38hi) are new antibody secreting cells identified in circulation. We used microarray to compare and contrast expressed genes between these two cell population
Publication Title
Distinctions among Circulating Antibody-Secreting Cell Populations, Including B-1 Cells, in Human Adult Peripheral Blood.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Objective: To study the physiological role of eosinophils in the GI tract and lung under homeostatic conditions,
Publication Title
The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The Ets family transcription factor PU.1 is essential for the development and maintenance of several hematopoietic lineages. In the thymus, PU.1 is expressed only in the early ETP/DN1, DN2a and DN2b stages of development. While PU.1 deletion in multipotent precursors leads to a complete block in T-cell development its function in the intrathymic stages in which it is expressed remains undetermined. The goal of this expression profiling study was to determine if PU.1 regulates the expression of T-lineage genes during the early stages of development. To do this, we generated the PU.1-Eng construct which expresses a fusion protein containing the DNA binding ETS domain of PU.1 (aas 159-260) fused to the obligate repressor domain (aas 1-298) of the Drosophila engrailed protein. The PU.1-ETS construct only expresses the ETS domain of PU.1 (aas 159-260) and serves as a control. Fetal liver precursors were isolated from e14.5 embryos and co-cultured with OP9-DL1 cells in the presence of IL-7 and Flt3L (5 ng/ml each) for 4 days to obtain FLDN1, DN2a and DN2b cells. These were infected with vector only, PU.1-ETS and the PU.1-Eng constructs and DN2 cells were sorted after 20 hours of infection. Total RNA was isolated from these cells and polyA+ fraction was used to prepare libraries for high throughput sequencing. Libraries prepared from 2 independent sets of samples were subjected to non-strand specific single-end sequencing. Overall design: Two sets of samples generated from fetal liver precursor derived DN2 cells expressing PU.1-ETS and PU.1-Eng constructs were used for expression profiling. The LZRS retroviral vector, without any insert, was used to generate the vector control dataset.
Publication Title
Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina Genome Analyzer II
Description
Both immunodeficient and wild type NOD mice exhibit defects in control of early T-cell development in the thymus. We show that Rag1-deficient NOD mice fail to enforce both the b-selection checkpoint and an earlier T-cell commitment checkpoint, based on genome-wide genetic and transcriptome analyses. A major QTL peak for the checkpoint breakthrough phenotype mapped to the diabetes susceptibility Idd9/11 region, as confirmed by congenic mouse analysis. Genome-wide RNA deep-sequencing revealed two classes of differences between NOD and B6 Rag1-deficient thymocytes: first, effects of genetic background prior to breakthrough, and second, effects of the breakthrough itself. These genotypes differentially express numerous signal transduction genes, prominently tyrosine kinase and actin-binding genes, some located within QTL regions. Emerging NOD breakthrough cells depart from the expected DN3 phenotype by expressing many stem cell-associated proto-oncogenes, such as Lmo2, Hhex, Lyl1, and Kit which are normally repressed earlier, and by illegitimate activation of post-b-selection genes like Cd2, Cd5, and Cd4. Co-expression of stem cell and T-cell genes persists in thymic lymphoma cells that emerge with high penetrance in these mice. These results imply that NOD thymocytes have defects that can collapse regulatory boundaries at two early T-cell checkpoints, which may predispose them to leukemia and autoimmunity. Overall design: Genetic and transcriptome analyses of early T-cell checkpoint failure and leukemia initiation in Rag1-deficient NOD mice
Publication Title
Loss of T cell progenitor checkpoint control underlies leukemia initiation in Rag1-deficient nonobese diabetic mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Gallus gallus
- 29 Downloadable Samples
- Illumina HiSeq 2500
Description
Climate change and disease have large negative impacts on poultry production, but little is known about the interactions of responses to these stressors in chickens. Fayoumi (heat and disease resistant) and broiler (heat and disease susceptible) chicken lines were stimulated at 22 days of age, using a 2x2x2 factorial design including: breed (Fayoumi or broiler), inflammatory stimulus [lipopolysaccharide (LPS) or saline], and temperature (35°C or 25°C). Transcriptional changes in spleens were analyzed using RNA-sequencing on the Illumina HiSeq 2500. Thirty-two individual cDNA libraries were sequenced (four per treatment) and an average of 22 million reads were generated per library. Stimulation with LPS induced more differentially expressed genes (DEG, log2 fold change = 2 and FDR = 0.05) in the broiler (N=283) than the Fayoumi (N=85), whereas heat treatment resulted in fewer DEG in broiler (N=22) compared to Fayoumi (N=107). The double stimulus of LPS+heat induced the largest numbers of changes in gene expression, for which broiler had 567 DEG and Fayoumi had 1471 DEG of which 399 were shared between breeds. Further analysis of DEG revealed pathways impacted by these stressors such as Remodelling of Epithelial Adherens Junctions due to heat stress, Granulocyte Adhesion and Diapedesis due to LPS, and Hepatic Fibrosis/Hepatic Stellate Cell Activation due to LPS+heat. The genes and pathways identified provide deeper understanding of the response to the applied stressors and may serve as biomarkers for genetic selection for heat and disease tolerant chickens. Overall design: At 22 days of age, divergent chicken breeds (Fayoumi and broiler) were treated with a thermal treatment (heat stress at 35C, or thermoneutral at 25C as a control) for 3.5 hours, then stimulated subcutaneously with an inflammatory stimulus (LPS, or saline as a control) for another 3.5 hours. Chickens were euthanized and spleens were harvested. A total of 32 indivudally coded cDNA libraries were prepared using TruSeq v2 library preparation kit which selects for polyA mRNA. In this 2x2x2 full factorial design with the factors of breed, thermal treatment, and inflammatory stimulus, there were a total of 8 treatment groups. Each treatment group had a total of 4 animal biological replicates. Therefore, a total of 32 individual barcoded samples were sequenced. A total of 8 individually barcoded cDNA libraries were sequenced per lane using the HiSeq Illumina 2500, and we used 4 lanes total. Reads were mapped to Galgal 2.0.
Publication Title
Unique genetic responses revealed in RNA-seq of the spleen of chickens stimulated with lipopolysaccharide and short-term heat.
Sample Metadata Fields
Subject
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