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GSE58644
Homo sapiens
319 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Breast carcinoma (BC) have been extensively profiled by high-throughput technologies for over a decade, and broadly speaking, these studies can be grouped into those that seek to identify patient subtypes (studies of heterogeneity) or those that seek to identify gene signatures with prognostic or predictive capacity. The shear number of reported signatures has led to speculation that everything is prognostic in BC. Here we show that this ubiquity is an apparition caused by a poor understanding of the inter- relatedness between subtype and the molecular determinants of prognosis. Our approach constructively shows how to avoid confounding due to a patient's subtype, clinicopathological or treatment profile. The approach identifies patients who are predicted to have good outcome at time of diagnosis by all available clinical and molecular markers, but who experience a distant metastasis within five years. These inherently difficult patients (~7% of BC) are prioritized for investigations of intra-tumoral heterogeneity.
Publication Title
The prognostic ease and difficulty of invasive breast carcinoma.
Sample Metadata Fields
Age, Disease stage, Time
View Samples- Gallus gallus
- 6 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
Modern functional genomic approaches may help to better understand the molecular events involved in tissue morphogenesis and to identify molecular signatures and pathways. We have recently applied transcriptomic profiling to evidence molecular signatures in the development of the normal chicken chorioallantoic membrane and in tumor engrafted on the CAM. We have now extended our studies by performing a transcriptome analysis in the wound model of the chicken CAM which is another relevant model of tissue morphogenesis. To induce granulation tissue formation, we performed wounding of the chicken CAM and compared gene expression to normal CAM at the same stage of development. Matched control samples from the same individual were used. We observed a total of 282 genes up-regulated and 44 genes downregulated assuming a false-discovery rate at 5 % and a fold change > 2. Furthermore, bioinformatics analysis lead to the identification of several categories that are associated to organismal injury, tissue morphology, cellular movement, inflammatory disease, development and immune system. Endothelial cell data filtering leads to the identification of several new genes with an endothelial cell signature. In summary, the chick chorioallantoic wound model allows the identification of gene signatures involved in granulation tissue formation and neoangiogenesis. This may constitute a fertile ground for further studies.
Publication Title
Gene signatures in wound tissue as evidenced by molecular profiling in the chick embryo model.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
Background. Primary cilia (PC) are solitary antennae present at the cell surface. These non-motile cilia play an important role in organ development and tissue homeostasis through the transduction of the Hedgehog (Hh) signaling pathway. We recently revealed the presence of PC in the epithelium of the developing epididymis, an organ of the male reproductive system whose dysfunction triggers male infertility. Acknowledging that systemic blockade of the Hh pathway trigger epididymal dysfunctions in vivo, our main goals were 1) to portray the epididymal Hh environment, 2) to determine the direct responsiveness of epididymal epithelial cells to Hh, and 3) to define the contribution of PC to the transduction of this pathway. Results. The Hh ligands Indian and Sonic hedgehog (Ihh and Shh) were respectively located in principal and clear cells of the mouse epididymis by immunofluorescent staining. The propensity of epididymal principal cells to respond to Hh signaling was assessed on immortalized epididymal DC2 cells by western-blot, confocal imaging and 3D-reconstruction. Our results indicate that epididymal principal cells secrete Ihh and expose PC that co-localize with the conventional acetylated tubulin/Arl13b ciliary markers, as well as with GLI3 Hh signaling factor. Gene expression microarray profiling indicated that the expression of 43 and 248 genes was respectively and significantly modified following pharmacological treatment of DC2 cells with the Hh agonist SAG (250 nM) or the Hh antagonist cyclopamine (20 µM) compared with the control. Among Hh target genes identified, 6.7 % presented perfect matches for GLI-transcription factor consensus sequences, and the majority belonged to interferon-dependent immune response and lipocalin 2 pathways. Finally, the contribution of epididymal PC to the transduction of canonical Hh pathway was validated by ciliobrevinD treatment, which induced a significant decrease of PC length and the expressional reduction of Hh signalling targets. Conclusions. All together our data indicate that PC from epithelial principal cells regulate gene expression profile through a possible autocrine Hh signaling. This provides new hypotheses regarding the potential contribution of PC and Hh signaling in intercellular cross-talk and immunological regulation of the epididymis.
Publication Title
Hedgehog signaling pathway regulates gene expression profile of epididymal principal cells through the primary cilium.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
Illumina HiSeq 2500
Description
In the central nervous system (CNS), the microRNAs (miRNAs), small endogenous RNAs exerting a negative post-transcriptional regulation on mRNAs, are involved in major functions, such as neurogenesis, and synaptic plasticity. Moreover, they are essential to define the specific transcriptome of the tissues and cell types. However, few studies were performed to determine the miRNome of the different structures of the rat CNS, even through rat is a major model in neuroscience. We determined the miRNome profile of the hippocampus, the cortex, the striatum, the spinal cord and the olfactory bulb, by small RNA-Seq. We found a total of 365 known miRNAs' and 90 novel miRNAs expressed in the CNS of the rat. Novel miRNAs seemed to be important in defining structure-specific miRNomes. Differential analysis showed that several miRNAs were specifically enriched/depleted in these CNS structures. Then, we correlated miRNAs' expression with the expression of their mRNA targets by mRNA-Seq. This analysis suggests that the transcriptomic identity of each structure is regulated by specific miRNAs. Altogether, these results suggest the critical role played by these enriched/depleted miRNAs in the functional identities of CNS structures. Overall design: miRNA and mRNA profile of 5 structures of the central nervous system of rat, for each structurewe analyzed three biological replicates
Publication Title
Small RNA-Seq reveals novel miRNAs shaping the transcriptomic identity of rat brain structures.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 4000
Description
The overall aim of this experiment was to identify specific genes and molecular pathways regulated by ML290, a small molecule agonist of the relaxin receptor, RXFP1, in the context of liver fibrosis. Overall design: Whole transcriptome mRNA sequencing of transformed LX-2 cells using HiSeq platforms with paired-end 150 bp (PE 150) sequencing strategy, with four biological replicates in each treatment group.
Publication Title
Therapeutic effects of a small molecule agonist of the relaxin receptor ML290 in liver fibrosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
A "Cartes d'Identite des Tumeurs" (CIT) project from the french Ligue Nationale Contre le Cancer (<a href="http://cit.ligue-cancer.net" target="_blank">http://cit.ligue-cancer.net</a>). 104 samples; Affymetrix U133A micro-arrays.<br></br> <br></br> Ninety two patients with T-ALL were diagnosed and treated at Saint-Louis hospital, Paris. Seven patients were studied at diagnosis and relapse (total 99 T-ALL samples). There were 56 children (median age 9 years old; range 1 to 16), and 36 adults (median age 27; range 17 to 66). Informed consent was obtained from the patients and/or relatives. T-ALL diagnosis was based on morphological and immunophenotypical criteria using flow cytometry and an extended monoclonal antibody panel.<br></br> <br></br> Using a combination of molecular cytogenetic and large-scale expression analysis in human T-ALL, we identified and characterized a new recurrent chromosomal translocation, targeting the major homeobox gene cluster HOXA and the TCRB locus. Specific quantitative PCR analysis showed that the expression of the whole HOXA gene cluster was dramatically dysregulated in the HOXA-rearranged cases, and also in MLL and CALM-AF10-related T-ALL cases, strongly suggesting that HOXA genes are oncogenic in these leukemias. Inclusion of HOXA-translocated cases in a general molecular portrait of 92 T-ALL based on large-scale expression analysis shows that this rearrangement defines a new homogeneous subgroup, which shares common biological networks with the TLX1 and TLX3-related cases. Since T-ALLs derive from T-cell progenitors, expression profiles of the distinct T-ALL subgroups were analyzed with respect to those of normal human thymic sub-populations. Inappropriate utilization or perturbation of specific molecular networks involved in thymic differentiation was detected. Moreover, we found a significant association between T-ALL oncogenic subgroups and ectopic expression of a limited set of genes, including several developmental genes, namely HOXA, TLX1, TLX3, NKX3-1, SIX6 and TFAP2C. These data strongly support the view that the abnormal expression of developmental genes, including the prototypical homeobox genes HOXA, is critical in T-ALL oncogenesis.<br></br> <br></br> Project Leader: <br></br> FranC'ois Sigaux<br></br> Institut Universitaire d'Hematologie<br></br> Hopital Saint Louis, Paris, France<br></br> <br></br> Data submission:<br></br>Fabien Petel
Publication Title
HOXA genes are included in genetic and biologic networks defining human acute T-cell leukemia (T-ALL).
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Systemic lupus erythematosous (SLE) is an autoimmune disease with an important clinical and biological heterogeneity. B lymphocytes appear central to the development of SLE which is characterized by the production of a large variety of autoantibodies and hypergammaglobulinemia. In mice, immature B cells from spontaneous lupus prone animals are able to produce autoantibodies when transferred into immunodeficient mice, strongly suggesting the existence of intrinsic B cell defects during lupus. In order to approach these defects in humans, we compared the peripheral B cell transcriptomes of quiescent lupus patients to normal B cell transcriptomes.
Publication Title
B cell signature during inactive systemic lupus is heterogeneous: toward a biological dissection of lupus.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 65 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transplant recipients spontaneously accepting their grafts in the absence of immunosuppression demonstrate the feasibility of attaining allograft tolerance in humans. Previous studies have identified blood transcriptional and cell phenotypic markers specific for either liver or kidney tolerant recipients, but the two settings have not been directly compared yet employing the same platforms. To identify potential similarities in immune parameters between recipients tolerant to different organs, we analyzed blood samples from tolerant and non-tolerant liver and kidney recipients employing whole genome expression microarrays. Tolerant and non-tolerant liver and kidney recipients differed in their peripheral blood expression patterns, but no significant overlap was observed between the two datasets. This was confirmed at the functional level by employing gene set enrichment analysis.The lack of obvious similarities in immune parameters associated with liver and kidney tolerant recipients implies the involvement of different mechanisms in the two settings and argues against the existence of a common immunological constant of spontaneous operational tolerance in clinical transplantation.
Publication Title
Comparison of transcriptional and blood cell-phenotypic markers between operationally tolerant liver and kidney recipients.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The indisputable role of epigenetics in cancer and the fact that epigenetic alterations can be reversed have favored development of epigenetic drugs. In this study, we have design and synthesize potent novel, selective and reversible chemical probes that simultaneously inhibit the G9a and DNMTs methyltransferase activity. In vitro treatment of hematological neoplasia (Acute Myeloid Leukemia-AML, Acute Lymphoblastic Leukemia-ALL and Diffuse Large B-cell Lymphoma-DLBCL) with the lead compound CM-272, inhibited cell proliferation and promoted apoptosis, inducing interferon stimulated genes and immunogenic cell death. CM-272 significantly prolonged survival of AML, ALL and DLBCL xenogeneic models. Our results represent the discovery of first-in-class dual inhibitors of G9a/DNMTs and establish this chemical series, as a promising therapeutic tool for unmet needs in hematological tumors.
Publication Title
Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies.
Sample Metadata Fields
Cell line, Treatment
View Samples