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Homo sapiens
6 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Tumor growth and metastasis is controlled by paracrine signaling between cells of the tumor microenvironment and malignant cells. Cancer-associated fibroblasts (CAFs), are functionally important components of the tumor microenvironment. Although some steps involved in the cross-talk between these cells are known, there is still a lot that is not clear. Thus, the addition of, the consideration of microenvironment in the development of the disease, to the clinical and pathological procedures (currently admitted as the consistent value cancer treatments) could lay the foundations for the development of new treatment strategies to control the disease.
Publication Title
Functional heterogeneity of cancer-associated fibroblasts from human colon tumors shows specific prognostic gene expression signature.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Snail1 transcriptional factor is essential for triggering epithelial-to-mesenchymal transition (EMT) and inducing tumor cell invasion. We report here that Snail1 plays also a key role in tumor associated fibroblasts since is necessary for enhancement by these cells on epithelial cells tumor invasion. Snail1 expression in fibroblast requires signals derived from tumor cells such as TGF-b; reciprocally, in fibroblasts Snail1 organizes a complex program that favors collective invasion of epithelial cells at least in part by the secretion of diffusible signaling molecules, such as prostaglandin E2. The capability of human or murine tumor-derived cancer associated fibroblasts to promote tumor invasion is associated to Snail1 expression and obliterated by Snail1 depletion. In vivo experiments show that tumor cells co-transplanted with Snail1 depleted fibroblasts show lower invasion than those xenografted with control fibroblasts. Finally Snail1 depletion in mice prevents the formation of breast tumors and decreased their invasion. Therefore, these results demonstrate that the role of Snail1 in tumor invasion is not limited to its effect in EMT but dependent on its expression in stromal fibroblasts where it orchestrates its activation and the crosstalk with epithelial cells.
Publication Title
Snail1-Dependent Activation of Cancer-Associated Fibroblast Controls Epithelial Tumor Cell Invasion and Metastasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Although skeletal muscle cells can be generated from human iPSCs, transgene-free protocols include only limited options for their purification and expansion. In this study we found that FACS-purified myogenic progenitors generated from healthy controls and Pompe disease iPSCs can be robustly expanded as much as 5 x 1011 fold. At all steps during expansion, cells could be cryopreserved or differentiated into myotubes with a high fusion index. In vitro, cells were amenable to maturation into striated and contractile myofibers. Insertion of the acid alpha glucosidase cDNA into the AAVS1 locus in iPSCs using CRISPR/cas9 prevented glycogen accumulation in myotubes generated from a patient with classic infantile Pompe disease. In vivo, the expression of human-specific nuclear and sarcolemmar antigens indicated that myogenic progenitors engraft into murine muscle to form human myofibers. This protocol is useful for modeling of skeletal muscle disorders and for using patient-derived, gene-corrected cells to develop cell-based strategies. Overall design: Myogenic progenitors were expanded for ~15 days and harvested either in proliferation conditions or after 4 days of differentiation as described previously (van der Wal et al., 2017b). RNA was extracted using the RNeasy minikit with DNAse treatment (Qiagen, Germantown, MD). Sequencing libraries were prepared using TruSeq Stranded mRNA Library Prep Kit (Illumina, San Diego, California, USA) according to the manufacturer's instructions. Libraries were sequenced on a HiSeq2500 sequencer (Illumina, San Diego, California, USA) in rapid-run mode according to the manufacturer's instructions. Reads 50 base-pairs in length were generated. The RNA-sequencing datasets listed in table S3 were downloaded and aligned with the datasets generated in this study using the 'new Tuxedo' pipeline (Pertea et al., 2016). The processed data file includes the analysis of 30 additonal Samples from other research groups, partly from GEO and partly from other sources such as ENCODE and ENA. The header table linked below lists the origin of the other Samples.
Publication Title
Large-Scale Expansion of Human iPSC-Derived Skeletal Muscle Cells for Disease Modeling and Cell-Based Therapeutic Strategies.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although heterochromatin is enriched with repressive traits, it is also actively transcribed, giving rise to large amounts of non-coding RNAs. Although these RNAs are responsible for the formation and maintenance of heterochromatin, little is known about how their transcription is regulated. Here we show that the Snail1 transcription factor represses pericentromeric transcription, acting through the H3K4 deaminase LOXL2. Since Snail1 plays a key role in the epithelial to mesenchymal transition (EMT), we analyzed the regulation of mouse heterochromatin transcription in this process. At the onset of EMT, one of the major structural heterochromatin proteins, HP1a, is transiently released from heterochromatin foci in a Snail1/LOXL2dependent manner during EMT, concomitantly with a down-regulation of major satellite transcription. Global transcriptome analysis indicated that ectopic expression of heterochromatin transcripts affects the transcription profile of EMT-related genes. Additionally, preventing the down-regulation of major satellite transcripts compromised the migratory and invasive behavior of mesenchymal cells. We propose that Snail1 regulates heterochromatin transcription through the histone-modifying enzyme, LOXL2, thus creating the favorable transcriptional state necessary for completing EMT.
Publication Title
Regulation of heterochromatin transcription by Snail1/LOXL2 during epithelial-to-mesenchymal transition.
Sample Metadata Fields
Cell line, Treatment
View Samples- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
A great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS.
Publication Title
Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression.
Sample Metadata Fields
Treatment
View Samples
GSE35600- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Gene expression from MDA-MB-231 cells shControl and shLOXL2.
Publication Title
Lysyl oxidase-like 2 (LOXL2) oxidizes trimethylated lysine 4 in histone H3.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Our results indicate that oxidation of TAF10 by LOXL2 induces its release from its promoters, leading to a block in TFIID-dependent gene transcription. Since TFIID complex is crucial for the expression of Nanog, Klf4, Sox2 and Oct4 and for maintaining the pluripotent state of embryonic stem cells, TAF10 oxidation by LOXL2 leads to inactivation of the pluripotency genes and a loss of pluripotent capacity in embryonic stem cells. Moreover, in vivo results demonstrate an essential role of LOXL2 in neural differentiation during zebrafish development: in the absence of LOXL2 the neural progenitor gene Sox2 is aberrantly overexpressed and neural differentiation is impaired.
Publication Title
LOXL2 Oxidizes Methylated TAF10 and Controls TFIID-Dependent Genes during Neural Progenitor Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
MicroRNAs serve to fine-tune gene expression and play an important regulatory role in tissue specific gene networks. The identification and validation of miRNA target genes in a tissue still poses a significant problem since the presence of a seed sequence in the 3´UTR of an mRNA and its expression modulation upon ectopic expression of the miRNA do not reliably predict regulation under physiological conditions. The chimeric oncoprotein EWS-FLI1 is the driving pathogenic force in Ewing Sarcoma. miR-17-92, one of the most potent oncogenic miRNAs, was recently reported to be the top EWS-FLI1 activated miRNA. Using a combination of AGO2 pull-down experiments by PAR-CLIP (Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) and of RNAseq upon miRNA depletion by ectopic sponge expression, we aimed to identify the targetome of miR-17-92 in Ewing sarcoma. Intersecting both datasets we found an enrichment of PAR-CLIP hits for members of the miR-17-92 cluster in the 3´UTRs of genes up-regulated in response to mir-17-92 specific sponge expression. Strikingly, approximately a quarter of these genes annotate to the TGFB/BMP pathway, the majority mapping downstream of SMAD signalling. Taken together, our findings shed light on the complex miRegulatory landscape of Ewing Sarcoma pointing miR-17-92 as a key node connected to TGFB/BMP pathway Overall design: mRNA profiles of a Ewings Sarcoma cellline (clone of A673 with inducible sh EWS-FLI1 knockdown) treated with microRNA sponges and controls
Publication Title
The role of miR-17-92 in the miRegulatory landscape of Ewing sarcoma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Transcription is a major obstacle for replication fork progression and a cause of genome instability. Such instability increases in mutants with a suboptimal assembly of the nascent messenger ribonucleo-protein particle (mRNP), as THO/TREX and some heterogeneous nuclear ribonucleoproteins (hnRNPs) mutants.
Publication Title
The Npl3 hnRNP prevents R-loop-mediated transcription-replication conflicts and genome instability.
Sample Metadata Fields
No sample metadata fields
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