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SRP060444
Drosophila melanogaster
4 Downloadable Samples
Illumina HiSeq 2000
Description
Comparing the transcriptome of wildtype and kdm5 mutant flies in normal conditions revealed a total of 4787 genes that were significantly downregulated and thus require KDM5 for their activation, and 3269 upregulated genes that are normally repressed by KDM5 (p<0.05, FDR <0.05). Because kdm5 mutants are sensitive to the oxidizer paraquat, we also carried out RNA-seq from wildtype and kdm5 mutant adults in oxidative stress conditions. Paraquat treatment of wildtype flies lead to the upregulation of 2481, and downregulation of 3103 genes Overall design: adult mRNA profiles of 1-3-days old wild type (WT) and kdm5 mutant under normal condition and oxitative stress were generated by deep sequencing, using Illumina HisSeq 2000.
Publication Title
The Histone Demethylase KDM5 Activates Gene Expression by Recognizing Chromatin Context through Its PHD Reader Motif.
Sample Metadata Fields
Sex, Specimen part, Subject
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- Populus trichocarpa
- 9 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
Embolism and the refilling of xylem vessels are intrinsic to the ability of plants to handle the transport of water under tension. While the formation of an embolized vessel is an abiotic process, refilling against the pressure gradient requires biological activity to provide both the energy and the water needed to restore xylem transport capacity.
Publication Title
Transcriptome response to embolism formation in stems of Populus trichocarpa provides insight into signaling and the biology of refilling.
Sample Metadata Fields
Specimen part, Treatment
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- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The present study was designed to identify Mkl1 target genes whose expression requires either the B1 site of Mkl1 and serum response factor (SRF), respectively, or the SAP domain of Mkl1. For this purpose, we obtained the transcriptomes of four stable 4T1 cell lines that either overexpress full length Mkl1-RFP (4T1-FL), Mkl1-RFP with a mutated SRF-interaction site (4T1-mutB1), Mkl1-RFP with a deletion of the SAP domain (4T1-SAP) or an empty vector encoding RFP alone (4T1 control).
Publication Title
Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Ewing Sarcoma is the second most common solid pediatric malignant neoplasm of the bone and soft tissue. Driven by EWS/Ets, or rarely variant, oncogenic fusions, Ewing Sarcoma is a biologically and clinically aggressive disease with a high propensity for metastasis. Our laboratory has previously identified the Jumonji-domain H3K9 me 1/2 histone demethylase KDM3A as a novel oncogene downstream of EWS/Fli1, the most common oncofusion in Ewing Sarcoma. Herein, we uncover a role for KDM3A in the promotion of Ewing Sarcoma metastasis.
Publication Title
The histone demethylase KDM3A, and its downstream target MCAM, promote Ewing Sarcoma cell migration and metastasis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The present study was designed to identify genes induced by irradiation in the 4T1 breast cancer model mimicking aggressive local relapse after radiotherapy. For this purpose, we obtained the transcriptomes of 4T1 tumors grown in either preirradiated (IRR+4T1) or non-irradiated (4T1) mammary tissue.
Publication Title
Mechanism of irradiation-induced mammary cancer metastasis: A role for SAP-dependent Mkl1 signaling.
Sample Metadata Fields
Specimen part
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- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Interactions between human keratinocytes and secreted factors from Staphylococcus aureus biofilm and planktonic cultures were investigated using microarray analysis.
Publication Title
Staphylococcus aureus Biofilm and Planktonic cultures differentially impact gene expression, mapk phosphorylation, and cytokine production in human keratinocytes.
Sample Metadata Fields
Treatment
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to generate a Drosophila model of intellectual disability caused by mutations in kdm5. RNA-seq was used to define the transcriptional defects of a mutation in Drosophila that is analogous to a human intellectual disability-associated allele, kdm5[A512p]. These data revealed a total of 1609 dysregulated genes, 778 of which were upregulated and 831 were downregulated. To determine whether these transcriptional defects were due to the loss of KDM5-induced histone demethylation, we also carried out RNA-seq from a enzymatic inactive strain, kdm5[Jmjc*]. These data revealed a striking similarity between the two datasets and suggest that the primary defect of KDM5[A512P] is loss of histone demethylase activity. Overall design: 3-5 day old adult heads from wildtype, kdm5[A512P] and kdm5[JmjC*] were used to generate RNA that was subsequently subjected to deep sequencing.
Publication Title
A Drosophila Model of Intellectual Disability Caused by Mutations in the Histone Demethylase KDM5.
Sample Metadata Fields
Specimen part, Subject
View Samples