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GSE38392
Homo sapiens
7 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Identification of druggable targets is a prerequisite for developing targeted therapies against Ewing sarcoma. We report the identification of Protein Kinase C Beta (PRKCB) as a protein specifically and highly expressed in Ewing sarcoma as compared to other pediatric cancers. Its transcriptional activation is directly regulated by the EWSR1-FLI1 oncogene. Getting insights in PRKCB activity we show that, together with PRKCA, it is responsible for the phosphorylation of histone H3T6, allowing global maintenance of H3K4 trimethylation on a variety of gene promoters. In the long term, PRKCB RNA interference induces apoptosis in vitro. More importantly, in xenograft mice models, complete impairment of tumor engraftment and even tumor regression were observed upon PRKCB inhibition, highlighting PRKCB as a most valuable therapeutic target. Deciphering PRKCB roles in Ewing sarcoma using expression profiling, we found a strong overlap with genes modulated by EWSR1-FLI1 and an involvement of RPKCB in regulating crucial signaling pathways. Altogether, we show that PRKCB may have two important independent functions and should be considered as highly valuable for understanding Ewing sarcoma biology and as a promising target for new therapeutic approaches in Ewing sarcoma.
Publication Title
Targeting the EWSR1-FLI1 oncogene-induced protein kinase PKC-β abolishes ewing sarcoma growth.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. However, very little is known about the transcriptional regulators involved in HC fate determination and differentiation. In this paper, we show that expression of three HC lineage-specific transcription factors: Gfi1, Pou4f3 and Atoh1, can induce a direct commitment towards HC fate during in vitro embryonic stem cell (ESC) differentiation. Induced HCs (iHCs) express numerous HC-specific genes and exhibit polarized membrane protusions reminiscent of stereociliary bundles.
Publication Title
Generation of sensory hair cells by genetic programming with a combination of transcription factors.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Metastatic melanoma is a deadly disease while non-metastatic melanoma and other cutaneous tumor types are usually cured with surgical removal of the primary tumors. This study evaluated gene expresion to determine if gene expression differences existed which would allow one to identify the metastatic tumors based on the expression of specific genes.
Publication Title
The gene expression profiles of primary and metastatic melanoma yields a transition point of tumor progression and metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
The goal of this study is to compare tumor-infiltrating antigen presenting cell populations by global transcriptome profiling (RNA-seq) to help further delineate sub-populations of infiltrating myeloid cells in tumor. Methods: Four tumor antigen presenting cell populations were sorted from digested B78chOVA (melanoma variant) tumors in biological triplicate Results: RNA was extracted from the 4 groups (n=3 per group) and prepared for RNAseq. Sequencing yielded ~405 million reads with an average read depth of 33.7 million reads/sample. Reads were then aligned to the mouse genome (UCSC mm10) and those that mapped uniquely to known mRNAs were used to assess differential expression. Overall design: Examination of four tumor infiltrating myeliod populations
Publication Title
Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
Intratumoral stimulatory dendritic cells (SDCs) play an important role in locally restimulating cytotoxic T cells and driving immune responses against cancer. However, the mechanisms that control SDC numbers remain poorly understood. In human melanoma, SDC numbers correlated with intratumoral expression of the gene encoding the cytokine FLT3LG, and we subsequently found in mouse and human tumors that this cytokine was predominantly produced by lymphocytes, notably including natural killer (NK) cells. NK cells stably formed conjugates with SDCs in the mouse tumor microenvironment (TME) and genetic and cellular ablation of NK cells in mice demonstrated their importance in regulation of SDC numbers through production of Flt3L. Although anti-PD-1 “checkpoint” immunotherapy for cancer largely targets T cells, we found that NK cells correlated with protective SDCs in human cancers, with patient responsiveness to anti-PD-1 immunotherapy, and with better overall survival. Our studies reveal that innate immune SDCs and NK cells cluster together as the best prognostic tool for T cell directed immunotherapy and that these innate cells are necessary for enhanced T cell tumor responses, suggesting this axis for novel therapies. Overall design: This dataset is n=11 biologically independent metastatic melanoma samples from patient tumors. There is no control dataset.
Publication Title
A natural killer-dendritic cell axis defines checkpoint therapy-responsive tumor microenvironments.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Escherichia coli release Extracellular Vesicles (EVs) which carry diverse molecular cargo. Pathogenic E.coli EVs contain virulence factors which assist during infection in the host in different mechanisms.The RNA cargo of E.coli EVs has not been assessed in their effect in the host. We used microarray data to asses and compare the global response of bladder cells to EV-RNA from pathogenic E.coli (Uropathogenic UPEC 536) and non-pathogenic E. coli (probiotic Nissle 1917)
Publication Title
Effect of the Extracellular Vesicle RNA Cargo From Uropathogenic <i>Escherichia coli</i> on Bladder Cells.
Sample Metadata Fields
Disease
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Microglia are brain immune cells that constantly survey their environment to maintain homeostasis. Enhanced microglial reactivity and proliferation are typical hallmarks of neurodegenerative diseases. Whether specific disease-linked microglial subsets exist during the entire course of neurodegeneration, including the recovery phase, is currently unclear. Taking a single-cell RNA-sequencing approach in a susceptibility gene-free model of nerve injury, we identified a microglial subpopulation that upon acute neurodegeneration shares a conserved gene regulatory profile compared to previously reported chronic and destructive neurodegeneration transgenic mouse models. Our data also revealed rapid shifts in gene regulation that defined microglial subsets at peak and resolution of neurodegeneration. Finally, our discovery of a unique transient microglial subpopulation at the onset of recovery may provide novel targets for modulating microglia-mediated restoration of brain health. Overall design: scRNA-Seq was performed on microglial cells isolated from the ipsilateral and contralateral ventral pons of CX3CR1GFP/wt mice that underwent unilateral facial nerve axotomy at 12 weeks of age. The contralateral ventral pons of un-operated 12-week-old CX3CR1GFP/wt was used as baseline control (Day 0 post nerve transection) for the analysis. Three replicates were used per time point (Day 0, 7 and 30 post axotomy). mCEL-Seq2 protocol was used for single cell sequencing (Hashimshony et al. 2016, Herman et al. 2018).
Publication Title
Unique microglia recovery population revealed by single-cell RNAseq following neurodegeneration.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
Recent research hints at an underappreciated complexity in pre-miRNA processing and regulation. Global profiling of pre-miRNA and its potential to increase understanding of the pre-miRNA landscape is impeded by overlap with highly-expressed classes of other non-coding RNA. Here we present a dataset excluding these RNA before sequencing through locked nucleic acids (LNA), greatly increasing pre-miRNA sequence counts with no discernable effects on pre-miRNA or mature miRNA sequencing. Analysis of profiles generated in total, nuclear, and cytoplasmic cell fractions reveals pre-miRNAs are subject to a wide range of regulatory processes involving loci-specific 3'- and 5'-end variation entailing complex cleavage patterns with co-occurring polyuridylation. Additionally, examination of nuclear-enriched flanking sequences of pre-miRNA, particularly those derived from polycistronic miRNA transcripts, provides insight into miRNA and miRNA-offset (moRNA) production. Our findings point to particularly intricate regulation of the let-7 family, introduce novel and unify known forms of pre-miRNA regulation and processing, and shed new light on the byproducts of miRNA processing pathways. none provided
Publication Title
pre-miRNA profiles obtained through application of locked nucleic acids and deep sequencing reveals complex 5'/3' arm variation including concomitant cleavage and polyuridylation patterns.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Maggot ES is known to induce wound healing in vivo to improve chronic wound repair. The effects have been studies at the protein and molecular level but never before at the transcriptional level.
Publication Title
The transcriptional responses of cultured wound cells to the excretions and secretions of medicinal Lucilia sericata larvae.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Unr (upstream of N-ras) is a cytoplasmic RNA-binding protein with cold shock domains, involved in regulation of messenger RNA stability and translation. To address the biological role of Unr, we inactivated the unr gene by homologous recombination in mice and embryonic stem (ES) cells. Embryos deficient for Unr die at mid-gestation, and the main phenotypic defects observed, growth deficiency and absence of neural tube closure, suggest a role of Unr in the balance proliferation/differentiation during early development. Here, we report that in Unr-null ES cell cultures, we observed a greater proportion of partially differentiated colonies, together with dispersed, refractile cells with stellate morphology, reminiscent of primitive endoderm (PrE) cells. DNA microarray, immunostaining, and RNA analyses revealed that Unr-null ES cells express a set of PrE markers, including the GATA6 transcription factor, a key inducer of PrE. Although Unr-deficient cells did not downregulate the pluripotency regulators Oct4, Nanog and Sox2, they grew more slowly than the wild-type lines, and their clonogenicity was lower. Silencing of Unr by RNA interference in ES E14 (129 genetic background) resulted in similar phenotypic and molecular changes as those observed in unr-/- ES cells (C57Bl/6 background). Finally, we show that ectopic expression of Unr in unr-/- ES cells partially reverses the endoderm-specific gene expression and the differentiation phenotype.
Publication Title
The RNA-binding protein Unr prevents mouse embryonic stem cells differentiation toward the primitive endoderm lineage.
Sample Metadata Fields
Specimen part, Treatment
View Samples