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SRP129026
Homo sapiens
29 Downloadable Samples
Illumina HiSeq 2500
Description
The adoptive transfer of chimeric antigen receptor- (CAR) modified T cells is revolutionizing the treatment of B cell malignancies and has the potential to be applied to other diseases. CARs redirect T cell specificity by linking an antigen recognition domain to T cell signaling modules comprised of CD3z to provide signal 1, and CD28 or 4-1BB to provide costimulation. CD28/CD3z and 4-1BB/CD3z CARs confer differences in effector function and cell fate that affect clinical efficacy and toxicity. These differences may result from activation of divergent transcriptional programs. To gain this insight, we analyzed changes in gene expression in stimulated and resting CD28/CD3z or 4-1BB/CD3z CAR T cells. CD28/CD3z CAR stimulation initiated more marked early transcriptional changes with greater fold increases in the expression of effector molecules including GZMB, IFNG, IL2, TNF, and IL6. Direct comparison of CD28/CD3z and 4-1BB/CD3z samples stimulated for 6 hours identified 1,673 differentially expressed genes. Of these, the memory T cell-associated genes KLF2, IL7R, and FAM65B were expressed at lower levels in CD28/CD3z CAR T cells. KLF2 and IL7R are FOXO transcription factor family targets and we found that FOXO4 expression was similarly reduced in CD28/CD3z CAR T cells. CD28/CD3z CAR stimulation induces an effector T cell-like transcriptional profile that may underlie the decreased persistence and increased risks of toxicities observed with CD28/CD3z CAR T cells in early clinical trials. Overall design: Purified CD28/CD3z and 4-1BB/CD3z CAR T cells were prepared from healthy donors and stimulated by incubation with anti-CAR beads, or left unstimulated by incubation with control beads. Total RNA was harvested 6 or 24 hours after treatment. Three biological replicates for each treatment condition were prepared, yielding 24 total samples for analysis. A42 and A44 denote 4-1BB/CD3z CARs, A43 and A45 denote CD28/CD3z CARs.
Publication Title
Phosphoproteomic analysis of chimeric antigen receptor signaling reveals kinetic and quantitative differences that affect cell function.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
peripheral blood samples of two leukemia patients in remission were profiled by single cell RNA sequencing approximately 1 year after receiving WT1 specific transgenic T cell therapy, at a time when patients were in clinical remission Overall design: single cell RNA sequencing of peripheral blood mononuclear cells
Publication Title
T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
In this study we addressed subclonal evolutionary process after treatment and subsequent relapse in multiple myeloma (MM) in a cohort of 24 MM patients treated either with conventional chemotherapy or with the proteasome inhibitor, bortezomib. Because MM is a highly heterogeneous disease coupled with a large number of DNA copy number alterations (CNAs) and loss of heterozygosity (LOH), we focused our study on the secondary genetic events: 1q21 gain, NF-kB activating mutations, RB1 and TP53 deletions, that seem to reflect progression. By using genome-wide high resolution SNP arrays we identified subclones with nonlinear complex evolutionary histories in a third of patients with myeloma, the relapse clone apparently derived from a minor subclone at diagnosis. Such reordering of the spectrum of genetic lesions during therapy is likely to reflect selection of genetically distinct subclones not initially competitive against the dominant population that survived chemotherapy, thrived and acquired new anomalies. In addition we found that emergence of minor subclones at relapse was significantly associated with bortezomib treatment. Altogether, these data support the idea of new strategy of future clinical trials in MM that would combine targeted therapy and subpopulations control to eradicate all myeloma subclones in order to obtain long-term remission.
Publication Title
Minor clone provides a reservoir for relapse in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Series GSE25262 patients on expression side.
Publication Title
Minor clone provides a reservoir for relapse in multiple myeloma.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used the microarrays to obtain the cancerous signatures of T-cell, B-cell, erythroid and megakaryoblastic leukemias in mice.
Publication Title
Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CF's physiopathology is poorly explained by the mutation alone. The oxydative stress could be a major factor of this illness . Study its impact on transcriptome's CF cell line could be ameliorate our understanding of the evolution of cystic fibrosis.
Publication Title
Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
The primary objective of the study was to investigate the uncoupling protein-1 (UCP1) associated features of human epicardial adipose tissue (eAT) using next generation deep sequencing. In addition, paired mediastinal adipose tissue (mAT) and subcutaneous adipose tissue (sAT) samples colleced from patients undergoing cardic surgeries at our center were included in the study. Overall design: Paired biopsies of eAT, mAT and sAT obtained from cardiac surgery patients (n=10), with specific criteria of high- and low- expression of UCP1 in eAT, were subjected to RNA sequencing. While the primary objective was to compare high- vs. low UCP1 expression in eAT, our study design further allowed us to investigate depot- and disease specific transcriptomic shifts in these patients. Specifically, 10 patients provided 30 samples (n = 10 each for eAT, mAT and sAT) that could be compared based on depot specificity (n = 10), obesity (n = 5 lean, n = 5 obese) and coronary artery disease (CAD) (n = 6 CAD, 4 = Non-CAD).
Publication Title
UCP1 expression-associated gene signatures of human epicardial adipose tissue.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2000
Description
A greater understanding of the molecular pathways that underpin the unique human hematopoietic stem and progenitor cell (HSPC) self-renewal program will improve strategies to expand these critical cell types for regenerative therapies. The post-transcriptional mechanisms guiding HSPC fate during ex vivo expansion have not been closely investigated. Using shRNA-mediated knockdown, we show that the RNA-binding protein (RBP) Musashi-2 (MSI2) is required for human HSPC self-renewal. Conversely, when overexpressed, MSI2 induces multiple pro-self-renewal phenotypes, including significant ex vivo expansion of short- and long-term repopulating cells through direct attenuation of aryl hydrocarbon receptor (AHR) signaling. Using a global analysis of MSI2-RNA interactions, we determined that MSI2 post-transcriptionally downregulates canonical AHR pathway components in cord blood HSPCs. Our study provides new mechanistic insight into RBP-controlled RNA networks that underlie the self-renewal process and provides evidence that manipulating such networks can provide a novel means to enhance the regenerative potential of human HSPCs expanded ex vivo. Overall design: 4 samples were used for RNA-seq (4 biological duplicate) including 2 sets of control samples (irrelvant shRNA kncok-downs)
Publication Title
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Although bodyguard (bdg), lacerata (lcr) and fiddlehead (fdh) mutations affect three unrelated genes, they trigger similar effects, i.e. ectopic organ fusion, increase of cuticle permeability. After performing cutin and wax analyses on these Arabidopsis thaliana mutants, which did not coincide with the putative enzyme functions, we hypothesised that these mutations trigger a complex response which may be visible at the transcriptional level.
Publication Title
Dissection of the complex phenotype in cuticular mutants of Arabidopsis reveals a role of SERRATE as a mediator.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The cancer stem cell model maintains that tumors are organized in a hierarchy driven by tumor initiating cells (TICs), and that patient survival inversely correlates with TIC gene expression. Here we generated a prognostic signature for HER2+ breast cancer from TICs purified from MMTV-Her2/Neu mammary tumors. TICs from this model, identified as Lin-:CD24+:JAG1- at a frequency of 2-5% by serial and single cell transplantation assays, showed elevated expression of proliferation genes and low expression of differentiation genes (compared to non-TIC fraction CD24- of the same tumor).
Publication Title
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα- breast cancer.
Sample Metadata Fields
Specimen part
View Samples