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GSE39843
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
- 36 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Acute Myeloid Leukemia (AML) is frequently associated with mutations of NPM1 (NPM1c+) and even if considered to be of better prognosis for younger patients, relapse is frequent and outcome remains poor for elder patients with a need for novel treatment strategies. Differentiation-based therapy by all trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) induce proteasomal degradation of NPM1c protein, NPM1 nuclear re localization, differentiation and apoptosis in NPM1c+ cells and blast clearance in relapsed/refractory AML patients. In line, the XPO1 inhibitor Selinexor showed similar results in vitro associated with down regulation of a specific HOX gene signature. BET inhibitors (BETi) OTX015 (MK-8628) and JQ1 yield antileukemic activity and here we demonstrate their effects in NPM1c+ leukemia cells compared to ATO+ATRA and Selinexor. Compared to ATO+ATRA and Selinexor, BRDi induced TP53 independent apoptosis, differentiation, proteasomal NPM1c degradation and nuclear relocalization in NPM1c+ OCI-AML3 cell line and to different extend in patient derived blast cells. As ATO+ATRA and Selinexor had significant biological activity in NPM1c+ cell line IMS-M2, these cells were resistant to BETi exposure, except for nuclear re localization of NPM1 which is a general phenomenon upon treatment with all three drug types. Gene profiling revealed that BRDi downregulate a BRD specific core gene signature in OCI-AML3 and IMS-M2 cells but IMS-M2 cells yield a transcriptional resistance signature including upregulation of the Wnt/beta-catenin pathway. HOX gene clusters in OCI-AML3 cells and IMS-M2 cells are heterogeneously regulated by BETi and are down regulated by ATO+ATRA in line with results reported for Selinexor treatment. Taken together, our preclinical results encourage clinical testing of ATO+ATRA, Selinexor and BRDi in NPM1c+ AML patients.
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Compound
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Invariant natural killer T cells (iNKT) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) and producing IL-17 represent a minor subset of CD1d-restricted iNKT cells (iNKT17) in C57BL/6J (B6) mice. We aimed in this study to define the reasons for their low distribution and the sequence of events accompanying their normal thymic development. We found that RORγt+ iNKT cells have higher proliferation potential and a greater propensity to apoptosis than RORγt- iNKT cells. These cells do not likely reside in the thymus indicating that thymus emigration, and higher apoptosis potential, could contribute to RORγt+ iNKT cell reduced thymic distribution. Ontogeny studies suggest that mature HSAlow RORγt+ iNKT cells might develop through developmental stages defined by a differential expression of CCR6 and CD138 during which RORγt expression and IL-17 production capabilities are progressively acquired. Finally, we found that RORγt+ iNKT cells perceive a strong TCR signal that could contribute to their entry into a specific Th17 like developmental program influencing their survival and migration. Overall, our study proposes a hypothetical thymic developmental sequence for iNKT17 cells, which could be of great use to study molecular mechanisms regulating this developmental program.
Publication Title
Characterization of the developmental landscape of murine RORγt+ iNKT cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 142 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Correlates of immune mediated protection to most viral and cancer vaccines are still unknown. This impedes the development of novel vaccines to incurable diseases such as HIV and cancer. In this study, we have used functional genomics and polychromatic flow cytometry to define the signature of the immune response to the yellow fever (YF) vaccine 17D (YF17D) in a cohort of forty volunteers followed for up to one year after vaccination. We show that immunization with YF17D leads to an integrated immune response that includes several effector arms of innate immunity including complement, the inflammasome and interferons, as well as adaptive immunity as shown by an early T cell response followed by a brisk and variable B cell response. Development of these responses is preceded, as demonstrated in three independent vaccination trials and in a novel in vitro system of primary immune responses (Modular IMmune In vitro Construct (MIMIC) system), by the coordinated up-regulation of transcripts for specific transcription factors including STAT1, IRF7 and ETS2 that are upstream of the different effector arms of the immune response. These results clearly show that the immune response to a strong vaccine is preceded by coordinated induction of masters transcription factors, that lead to the development of a broad, polyfunctional and persistent immune response that integrates all effector cells of the immune system.
Publication Title
Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Classical CD16- versus intermediate/non-classical CD16+ monocytes differ in their homing potential and immunological functions; but whether they differentiate into dendritic cells (DC) with distinct contributions to immunity against bacterial/viral pathogens remains poorly investigated. Here, we employed a systems biology approach to identify differences between CD16+ and CD16- monocyte-derived DC (MDDC) with potential clinical relevance
Publication Title
CD16<sup>+</sup> monocytes give rise to CD103<sup>+</sup>RALDH2<sup>+</sup>TCF4<sup>+</sup> dendritic cells with unique transcriptional and immunological features.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Estrogen receptors (ERs), which mediate the proliferative action of estrogens in breast cancer cells, are ligand-dependent transcription factors that regulate expression of their primary target genes through several mechanisms. In addition to direct binding to cognate DNA sequences, ERs can be recruited to DNA through other transcription factors (tethering), or affect gene transcription through modulation of signaling cascades by non-genomic mechanisms of action. To better characterize the mechanisms of gene regulation by estrogens, we have identified more than 700 putative primary and more than 1500 putative secondary target genes of estradiol in MCF7 cells through microarray analysis performed in the presence or absence of the translation inhibitor cycloheximide.
Publication Title
Mechanisms of primary and secondary estrogen target gene regulation in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
dB/dB mice develop different kidney pathologies resulting from high body weight. We seek to better understand the mechanisms of this kidney damage in proximal tubules. We isolated RNA from proximal tubules of different groups of mice, and we seek to understand how the anti-oxidant enzyme catalase may regulate kidney damage in this model.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Expression data from xenograft in BALB/c 6-wk-old nude mice with PC3 prostate cancer cells stably expressing PML or a vector control after treatment of the mice with palbociclib (100mg/kg/day diluted in sodium lactate 50mM pH4 given by gavage) during 5 consecutive days
Publication Title
A CDK4/6-Dependent Epigenetic Mechanism Protects Cancer Cells from PML-induced Senescence.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We previously demonstrated that Th1Th17 cells are highly permissive to HIV-1, whereas Th1 cells are relatively resistant. Here, we investigated molecular mechanisms underlying these differences. Superior HIV replication in Th1Th17 vs. Th1 cells was regulated by entry and post-entry mechanisms.
Publication Title
Transcriptional profiling reveals molecular signatures associated with HIV permissiveness in Th1Th17 cells and identifies peroxisome proliferator-activated receptor gamma as an intrinsic negative regulator of viral replication.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human peripheral blood monocytes (Mo) consist of subsets distinguished by expression of CD16 (FCGRIII) and chemokine receptors. Classical CD16- Mo express CCR2 and migrate in response to CCL2, while a minor CD16+ Mo subset expresses CX3CR1 and migrates into tissues expressing CX3CL1. CD16+ Mo produce pro-inflammatory cytokines and are expanded in certain inflammatory conditions including HIV infection.
Publication Title
Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+ and CD16- monocyte subsets.
Sample Metadata Fields
Specimen part
View Samples