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Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
TRIM24 and TRIM33 interact to form a corepressor complex that suppresses murine hepatocellular carcinoma (HCC). TRIM24 and TRIM33 cooperatively repress retinoic acid receptor dependent activity of VL30 retro-transposons in hepatocytes in vivo. In TRIM24 knockout hepatocytes, VL30 long terminal repeats (LTRs) generate enhancer (e)RNAs and act as surrogate promoter and enhancer elements deregulating expression of neighbouring genes. We show that a VL30 LTR-derived eRNA is essential to activate the lipocalin 13 gene in hepatocytes in vivo. A further consequence of VL30 de-repression is the accumulation of retro-transcribed VL30 DNA in the cytoplasm of TRIM24-mutant hepatocytes and activation of the viral defence/interferon response. VL30 activation therefore modulates gene expression via the enhancer activity of the LTRs and by activation of the interferon response. Both of these processes are genetically linked to HCC development suggesting that VL30 repression by TRIM24 plays an important role in tumour suppression. Overall design: RNA profiles in liver of wild type (WT) and Trim24-/- mice by deep sequencing using Illumina GAIIx.
Publication Title
Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pericryptal myofibroblasts in the colon and rectum play an important role in regulating the normal colorectal stem cell niche and facilitating tumour progression. Myofibroblasts have previously mostly been distinguished from normal fibroblasts only by the expression of smooth muscle actin (SMA). We now identify AOC3, a surface monoamine oxidase, as a new marker of myofibroblasts by showing that it is the target protein of the myofibroblast reacting monoclonal antibody (mAb), PR2D3. The normal and tumour tissue distribution and the cell line reactivity of AOC3 match that expected for myofibroblasts. We have shown that the surface expression of AOC3 is sensitive to digestion by trypsin and collagenase and that anti-AOC3 antibodies can be used for FACS sorting of myofibroblasts obtained by non-enzymatic procedures. Whole genome microarray mRNA expression profiles of myofibroblasts and skin fibroblasts revealed four additional genes that are significantly expressed differentially between these two cell types; NKX2-3 and LRRC17 are expressed in myofibroblasts and SHOX2 and TBX5 in skin fibroblasts. Transforming Growth Factor (TGF) substantially down-regulated AOC3 expression in myofibroblasts but not in skin fibroblasts, in which it dramatically increased the expression of SMA. A knockdown of NKX2-3 in myofibroblasts caused a decrease of myofibroblast-related gene expression and an increased expression of the fibroblast associated gene, SHOX2, suggesting that NKX2-3 is a key mediator for maintaining myofibroblast characteristics. Our results show that colorectal myofibroblasts, as defined by the expression of AOC3, NKX2-3 and other markers, are a distinctly different cell type from TGF activated fibroblasts.
Publication Title
Myofibroblasts are distinguished from activated skin fibroblasts by the expression of AOC3 and other associated markers.
Sample Metadata Fields
Specimen part
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GSE31681- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cumulus cells (CCs) are biologically distinct from other follicular cells and perform specialized roles, transmitting signals within the ovary and supporting oocyte maturation during follicular development. The Affymetrix 3 IVT express protocol was used to prepare cRNA (one-cycle amplification) with a starting concentration of 100 ng of total RNA
Publication Title
Human cumulus cells molecular signature in relation to oocyte nuclear maturity stage.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 56 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
The 16p11.2 deletion and duplication syndromes have been associated with developmental delay and autism spectrum disorders, and a reciprocal effect on body mass index. Here we explored these links with new engineered mouse models carrying a deletion (Del/+) and duplication (Dup/+) of the whole 16p11.2 homologous Sult1a1-Spn region. On a pure genetic background, compared to wild-types, Del/+ mice carrying the deletion showed weight and adipogenesis deficits, hyperactivity, repetitive behaviors, and recognition memory deficits, whereas Dup/+ mice showed the opposite phenotypes and Del/Dup individuals displayed no changes. Alterations in social interaction were also observed in Del/+ and Dup/+ animals on a mixed genetic background.
Publication Title
Reciprocal Effects on Neurocognitive and Metabolic Phenotypes in Mouse Models of 16p11.2 Deletion and Duplication Syndromes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
A major impediment to the effective treatment of patients with PDAC (Pancreatic Ductal Adenocarcinoma) is the molecular heterogeneity of the disease, which is reflected in an equally diverse pattern of clinical responses to therapy. We developed an efficient strategy in which PDAC samples from 17 consecutively patients were obtained by EUS-FNA or surgery, their cells maintained as a primary culture and tumors as breathing tumors by xenografting in immunosuppressed mice. For these patients a clinical follow up was obtained. On the breathing tumors we studied the RNA expression profile by an Affymetrix approach. We observed a significant heterogeneity in their RNA expression profile, however, the transcriptome was able to discriminate patients with long- or short-time survival which correspond to moderately- or poorly-differentiated PDAC tumors respectively. Cells allowed us the possibility to analyze their relative sensitivity to several anticancer drugs in vitro by developing a chimiogram, like an antibiogram for microorganisms, with several anticancer drugs for obtaining an individual profile of drug sensitivity and as expected, the response was patient-dependent. Interestingly, using this approach, we also found that the transcriptome analysis could predict the sensitivity to some anticancer drugs of patients with a PDAC. In conclusion, using this approach, we found that the transcriptome analysis could predict the sensitivity to some anticancer drugs and the clinical outcome of patients with a PDAC.
Publication Title
Transcriptomic analysis predicts survival and sensitivity to anticancer drugs of patients with a pancreatic adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to detail the global gene expression signature of PDAC and to identify distinct up- and down-regulated transcripts in these tumors compared to control pancreas. We also established from this dataset the metabolic signature of PDAC in order to define new metabolic therapeutic target for pancreatic cancer.
Publication Title
Cholesterol uptake disruption, in association with chemotherapy, is a promising combined metabolic therapy for pancreatic adenocarcinoma.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic Ductal Adenocarcinoma (PDA) is a critical health issue in cancer field with little new therapeutic options. Several evidences support an implication of intra-tumoral microenvironment (stroma) on PDA progression. However, its contribution to the role of neuroplastic changes within pathophysiology and clinical course of PDA, mainly through tumor recurrence and neuropathic pain, remains unknown neglecting a putative therapeutic window. Here, we report that intra-tumoral microenvironment is a mediator of PDA Associated Neural Remodeling (PANR). With laser capture microdissection of stromal/tumoral compartment from human PDA followed by cDNA based microarray analyses we highlighted numerous factors expressed by stromal compartment that could impact on neuroplastic changes; among them, the Slit2/Robo axon guidance pathway. Using co-culture in vitro, we showed that stromal secreted Slit2 increases DRG neurite outgrowth and Schwann cells migration/proliferation by modulating N-Cadherin/-Catenin signaling. Importantly, Slit2/Robo signaling inhibition disrupts this stromal/neural connection. Finally, we revealed in vivo that Slit2 expression is correlated with neural remodeling within Human and mouse PDA. These results demonstrate the implication of microenvironment, through secretion of axon guidance molecule, in PANR. Furthermore, it provides rationale to investigate the disruption of stromal/neural compartment dialogue by using Slit2/Robo pathway inhibitors for treatment of pancreatic cancer recurrence and associated pain.
Publication Title
Stromal SLIT2 impacts on pancreatic cancer-associated neural remodeling.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
c-Myc controls more than 15% of genes responsible for proliferation, differentiation, and cellular metabolism in pancreatic as well as other cancers making this transcription factor a prime target for treating patients. The transcriptome of 55 patient derived xenografts show that 30% of them share an exacerbated expression profile of MYC transcriptional targets (MYC-high). This cohort is characterized by a high level of Ki67 staining, a lower differentiation state and a shorter survival time compared to the MYC-low subgroup. To define classifier expression signature, we selected a group of 10 MYC targets transcripts which expression is increased in the MYC-high group and 6 transcripts increased in the MYC-low group. We validated the ability of these markers panel to identify MYC-high patient-derived xenografts from both: discovery and validation cohorts as well as primary cells cultures from the same patients. We then showed that cells from MYC-high patients are more sensitive to JQ1 treatment compared to MYC-low cells, in both monolayer and 3D cultured spheroids, due to cell cycle arrest followed by apoptosis. Therefore, these results provide new markers and potentially novel therapeutic modalities for distinct subgroups of pancreatic tumors and may find application to the future management of these patients within the setting of individualized medicine clinics.
Publication Title
Gene expression profiling of patient-derived pancreatic cancer xenografts predicts sensitivity to the BET bromodomain inhibitor JQ1: implications for individualized medicine efforts.
Sample Metadata Fields
Disease
View Samples