Filters
Technology
Platform
Homo sapiens
35 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Soft tissue sarcomas are a diverse set of fatal human tumors where few agents have demonstrable clinical efficacy, with the standard therapeutic combination of doxorubicin and ifosfamide showing only a 25-30% response rate in large multi-institutional trials. Although liposarcomas are the most common histological form of adult soft tissue sarcomas, research in this area is severely hampered by the lack of experimentally tractable in vitro model systems. To this end, here we describe a novel in vitro model for human pleomorphic liposarcoma. The cell line (LS2) is derived from a pleomorphic liposarcoma that utilizes Alternative Lengthening of Telomeres (ALT) mechanism of telomere maintenance, which may be particularly important in modulating the response of this tumor type to DNA damaging agents. We present detailed baseline molecular and genomic data, including genome wide copy number and transcriptome profiles, for this model compared to its parental tumor and a panel of liposarcomas covering multiple histologies. The model has retained essentially all of the detectable alterations in copy number that are seen in the parental tumor, and shows molecular karyotypic and expression profiles consistent with pleomorphic liposarcomas. We also demonstrate the utility of this model, together with two additional human liposarcoma cell lines, to investigate the relationship between topoisomerase 2A expression and the sensitivity of ALT-positive liposarcomas to doxorubicin. This model, together with its associated baseline data, provide a powerful new tool to develop treatments for this clinically poorly-tractable tumor, and to investigate the contribution that ALT makes to modulating sensitivity to DNA damaging chemotherapeutic agents such as doxorubicin.
Publication Title
Doxorubicin resistance in a novel in vitro model of human pleomorphic liposarcoma associated with alternative lengthening of telomeres.
Sample Metadata Fields
Cell line
View Samples
GSE55129- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Purpose:The goals of this study are to understand the mechanisms underlying reduced self-renewal and loss of pluripotency by depletion of Rif1.
Publication Title
Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
The cyclin-dependent kinase inhibitor p21WAF1/Cip1 is the prototype downstream effector of the tumor suppressor protein p53. Yet, evidence from human cancer and mice models, imply that p21WAF1/Cip1, under certain conditions, can exercise oncogenic activity. The mechanism behind this behavior is still obscure. Within this context we unexpectedly noticed, predominantly in p53 mutant human cancers, that a subset of highly atypical cancerous cells expressing strongly p21WAF1/Cip1 demonstrated also signs of proliferation. This finding suggests either tolerance to high p21WAF1/Cip1 levels or that p21WAF1/Cip1 per se guided a selective process that led to more aggressive off-springs. To address the latter scenario we employed p21WAF1/Cip1-inducible p53-null cellular models and monitored them over a prolonged time period, using high-throughput screening means. After an initial phase characterized by stalled growth, mainly due to senescence, a subpopulation of p21WAF1/Cip1 cells emerged, demonstrating increased genomic instability, aggressiveness and chemo-resistance. At the mechanistic level unremitted p21WAF1/Cip1 production saturates the CRL4CDT2 and SCFSkp2 ubiquitin ligase complexes reducing the turn-over of the replication licensing machinery. Deregulation of replication licensing triggered replication stress fuelling genomic instability. Conceptually, the above notion should be considered when anti-tumor strategies are designed, since p21WAF1/Cip1 responds also to p53-independent signals, including various chemotherapeutic compounds.
Publication Title
Chronic p53-independent p21 expression causes genomic instability by deregulating replication licensing.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
IlluminaHiSeq2000
Description
Purpose: identify sites in endogenous mRNAs that are cut by KSHV SOX; Method: parallel analysis of RNA ends (PARE, following Zhai et al., 2014); Results: SOX cuts at discrete locations in mRNAs Overall design: human Xrn1 was knocked down in HEK293T cells by shRNAs or siRNAs to stabilize degradation fragments with free 5'' ends; GFP-SOX or GFP were transfected for ~24 hrs; total RNA samples were collected and subjected to PARE protocol (Zhai et al., 2014)
Publication Title
Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
To elucidated through an unbiased manner which genes and pathways are differentially regulated during mouse colonic inflammation followed by a tissue regeneration phase. In particular, we took advantage of the widely used dextran sodium sulfate (DSS)-induced model of colitis. This model is one of the few characterized by a phase of damage followed by a phase of regeneration. Therefore, this model gave the possibility to identify also sets of genes essential in the regeneration phase, a key step towards the resolution of the inflammation. In short, mice were exposed to DSS in the drinking water for 7 days, then allowed to recover for the following 7 days. During this period, we collected colonic tissue samples every second day to then be analyzed by RNA sequencing (RNA-seq). Next, we performed a RNA-seq analysis from colonic samples throughout the experiment and computed differentially expressed genes (DEGs) taking the complete kinetics of expression into consideration for p-value estimation using EdgeR. Overall design: C57BL/6J female mice were treated with 2.5% DSS in order to induce colinic inflammation. 2-3 animals were sacrificed at different time points when the colonic tissue was collected.
Publication Title
Conserved transcriptomic profile between mouse and human colitis allows unsupervised patient stratification.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Self-renewal of embryonic stem cells (ESCs) cultured in serum-LIF is incomplete with some cells initiating differentiation. While this is reflected in heterogeneous expression of naive pluripotency transcription factors (TFs), the link between TF heterogeneity and differentiation is not fully understood. Here we purify ESCs with distinct TF expression levels from serum-LIF cultures to uncover early events during commitment from nave pluripotency. ESCs carrying fluorescent Nanog and Esrrb reporters show Esrrb downregulation only in NANOGlow cells. Independent Esrrb reporter lines demonstrate that ESRRBnegative ESCs cannot effectively self-renew. Upon ESRRB loss, pre-implantation pluripotency gene expression collapses. ChIP-Seq identifies different regulatory element classes that bind both OCT4 and NANOG in ESRRBhigh cells. Class I elements lose NANOG and OCT4 binding in ESRRBnegative ESCs and associate with genes expressed preferentially in nave ESCs. In contrast, class II elements retain OCT4 but not NANOG binding in ESRRBnegative cells and associate with more broadly expressed genes. Therefore, mechanistic differences in TF function act cumulatively to restrict potency during exit from nave pluripotency.
Publication Title
Esrrb extinction triggers dismantling of naïve pluripotency and marks commitment to differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Expression profiling of normal NIH3T3 and transformed NIH3T3 K-ras cell lines grown for 72 hours in optimal glucose availability (25 mM glucose) or low glucose availability (1 mM). Low glucose induces apoptosis in transformed cells as compared to normal ones.
Publication Title
Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth.
Sample Metadata Fields
Cell line, Time
View Samples- Rattus norvegicus
- 11 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Background and Aims: It is well demonstrated that in the beta cell population of the pancreas there is a dynamic turnover, which results from the net balance of several processes; beta cell replication, apoptosis and neogenesis. These processes have been studied in partial pancreatectomy and glucagon-like peptide 1 treated animals, where an increase in pancreas regeneration has been observed. Similarly, sodium tungstate, which decreases hyperglycemia in several animal models of diabetes, promotes a rise in the beta cell mass of nSTZ and STZ animals. However, the molecular mechanisms underlying this pancreas regeneration remain unknown. Therefore the objective of this study is to identify which genes are up or down regulated in the increase of the beta cell population of STZ rats treated with sodium tungstate.
Publication Title
Molecular mechanisms of tungstate-induced pancreatic plasticity: a transcriptomics approach.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this analysis was to investigate the targets of the influenza A host shutoff ribonuclease PA-X. We profiled the relative levels of cellular RNAs in cells infected with influenza A virus (A/PuertoRico/8/1934 H1N1) comparing wild-type and mutants that make reduced levels of PA-X and/or make a truncated and inactive PA-X. We also profiled relative RNA levels in cells overexpressing wild-type PA-X or a catalytically inactive mutant (D108A). Overall design: for extopic expression, PA-X (from the A/PuertoRico/8/1934 H1N1 (PR8) strain) was expressed in A549 cells using a doxycyline-inducible transgene for 18 hrs; for infection, A549 cells were infected with the wild-type PR8 strain or mutant strain that carried mutations that reduce PA-X production or activity for 15 hrs. rRNA deplete RNA was subjected to high-throughput sequencing
Publication Title
The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Sample Metadata Fields
Treatment, Subject
View Samples