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GSE84827
Mus musculus
6 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
Foxp3+Tregcells are essential modulators of immune responses but under specific conditions can acquire inflammatory properties and potentially contribute to disease pathogenesis. Here we show that the transcription factor Blimp1 is a critical regulator of Foxp3+Treg functional plasticity. The intrinsic expression of Blimp1 was required to prevent Treg from producing Th17-associated cytokines and acquiring an inflammatory phenotype while preserving Foxp3 expression. Mechanistically, Blimp1 acts as a direct repressor of the Il17a/Il17f genes in Foxp3+Treg and binding of Blimp1 at this locus is associated with altered chromatin status, reduced binding the co-activator p300, unaltered binding of the Th17-asssociated transcription factor RORt and more abundant binding of IRF4, which was required for the production of IL17A in Blimp1-deficient Foxp3+Tregcells, as shown by IRF4 siRNA-mediated knockdown. Consistent with their capacity to produce inflammatory cytokines, Blimp1-deficient Foxp3+Treg exacerbate Th17-mediated inflammation in vivo indicating that Blimp1 is required to prevent Treg cells from acquiring pathogenic properties
Publication Title
Differential regulation of Effector and Regulatory T cell function by Blimp1.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 9 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in the CNC. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein.
Publication Title
Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Leukotriene E4 (LTE4) the most stable of the cysteinyl leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.
Publication Title
Leukotriene E4 is a full functional agonist for human cysteinyl leukotriene type 1 receptor-dependent gene expression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 288 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To identify new markers for minimal residual disease (MRD) detection in acute lymphoblastic leukemia (ALL), we compared genome-wide gene expression of lymphoblasts from 270 patients with newly diagnosed childhood ALL to that of normal CD19 CD10 B-cell progenitors (n=4). Expression of 30 genes differentially expressed by > 3-fold in at least 25% of cases of ALL (or 40% of ALL subtypes) was tested by flow cytometry in 200 B-lineage ALL and 61 nonleukemic BM samples, including samples containing hematogones. Of the 30 markers, 22 (CD44, BCL2, HSPB1, CD73, CD24, CD123, CD72, CD86, CD200, CD79b, CD164, CD304, CD97, CD102, CD99, CD300a, CD130, PBX1, CTNNA1, ITGB7, CD69, CD49f) were differentially expressed in up to 81.4% of ALL cases; expression of some markers was associated with the presence of genetic abnormalities. Results of MRD detection by flow cytometry with these markers correlated well with those of molecular testing (52 follow-up samples from 18 patients); sequential studies during treatment and diagnosis-relapse comparisons documented their stability. When incorporated in 6-marker combinations, the new markers afforded the detection of 1 leukemic cell among 105 BM cells. These new markers should allow MRD studies in all B-lineage ALL patients, and substantially improve their sensitivity.
Publication Title
New markers for minimal residual disease detection in acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Despite improved therapy, approximately one-fifth of children with acute T-lymphoblastic leukemia (T-ALL) succumb to the disease, suggesting unrecognized biologic heterogeneity that may contribute to drug resistance. We studied leukemic cells, collected at diagnosis, to identify features that could define this high-risk subgroup. A total of 139 patients with T-ALL were treated consecutively from 1992 to 2006 at this institution. Their leukemic cells were examined with multiparameter flow cytometry, single nucleotide polymorphism arrays and other methods of genomic analysis. Survival rates and probabilities of treatment failure were calculated for subgroups considered to have biologically distinct forms of T-ALL.
Publication Title
Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
Illumina HiSeq 2000
Description
The transcription factor T-bet induces differentiation of CD4+ T cells into the Th1 lineage and also allows for a degree of functional plasticity. Here, we show that T-bet acts through super-enhancers to recruit the elongation factor P-TEFb. Th1-specific genes are poised for activation in Th2 cells and P-TEFb recruitment activates transcriptional elongation. T-bet also induces extensive P-TEFb binding at super-enhancers, where it acts to stimulate enhancer RNA transcription. P-TEFb inhibition selectively blocks activation of lineage-specific genes and reverses Th1-associated retinitis pathology. T-bet-mediated recruitment of P-TEFb to super-enhancers at otherwise poised genes provides a model for how lineage-specifying factors promote differentiation towards specific cell fates whilst maintaining a degree of functional plasticity. Overall design: Strand-specific total and poly-A+ RNA-Seq in Th1 and Th2 cells from two independent donors
Publication Title
T-bet Activates Th1 Genes through Mediator and the Super Elongation Complex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 99 Downloadable Samples
- Illumina HiSeq 2000
Description
Assessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq. Overall design: 103 total samples from 63 unique patients. Clinical details were provided only for the 50 samples in current publication. However, all 103 samples were analyzed together.
Publication Title
Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets.
Sample Metadata Fields
Age, Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Metastasis is the leading cause of death for cancer patients. Consequently it is imperative that we improve our understanding of the molecular mechanisms that underlie progression of tumour growth towards malignancy. Advances in genome characterisation technologies have been very successful in identifying commonly mutated or misregulated genes in a variety of human cancers. However the difficulty in evaluating whether these candidate genes drive tumour progression remains a major challenge. Using the genetic amenability of Drosophila melanogaster we generated tumours with specific genotypes in the living animal and carried out a detailed systematic loss-of-function analysis to identify conserved genes that enhance or suppress epithelial tumour progression. This enabled the discovery of functional cooperative regulators of invasion and the establishment of a network of conserved invasion suppressors. This includes constituents of the cohesin complex, which can either promote individual or collective invasion, depending on the severity of effect on cohesin function.
Publication Title
A Genetic Analysis of Tumor Progression in Drosophila Identifies the Cohesin Complex as a Suppressor of Individual and Collective Cell Invasion.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
A significant proportion of patients with oestrogen receptor (ER) positive breast cancers (BC) develop resistance to endocrine treatments (ET) and relapse with metastatic disease. Bone is the most common metastatic site in ER+ patients, however bone metastases are technically challenging to biopsy and analyse. Difficulties concern both tumour tissue acquisition and techniques for analysis and RNA extractions. Patient-derived xenografts (PDX) of BC bone metastases have not been reported yet. For the first time we established PDX models from bone metastatic biopsies of patients progressing on ET and treated by vertebroplasty. PDX models were analysed at transcriptomic level and compared to patient’s early primary tumours to identify new therapeutic targets associated with endocrine resistance in the metastatic setting.
Publication Title
PLK1 inhibition exhibits strong anti-tumoral activity in CCND1-driven breast cancer metastases with acquired palbociclib resistance.
Sample Metadata Fields
Disease, Disease stage, Treatment
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed RNAseq on l(3)mbt mutant somatic ovaries to gain a genome-wide view of tissue-specific gene expression changes in L(3)mbt-depleted somatic ovaries. Overall design: Examination of gene expression changes in mutant and control somatic ovaries.
Publication Title
L(3)mbt and the LINT complex safeguard cellular identity in the <i>Drosophila</i> ovary.
Sample Metadata Fields
Specimen part, Subject
View Samples