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GSE106581
Mus musculus
18 Downloadable Samples
Description
The cancer-risk associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long non-coding RNA CCAT2 in the highly amplified 8q24.21 region has been implicated in cancer predisposition, though causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by downregulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel disease-specific RNA mutation (named DNA-to-RNA allelic imbalance, DRAI) at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
Publication Title
Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA <i>CCAT2</i> induce myeloid malignancies via unique SNP-specific RNA mutations.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 2 Downloadable Samples
Description
MicroRNAs comprise 1-3% of all vertebrate genes, but their in vivo functions and mechanisms of action remain largely unknown. Zebrafish miR-430 is expressed at the onset of zygotic transcription and regulates morphogenesis during early development. Using a microarray approach and in vivo target validation, we find that miR-430 directly regulates several hundred target mRNAs. Targets are highly enriched for maternal mRNAs that accumulate in the absence of miR-430. We also show that miR-430 accelerates the deadenylation of target mRNAs. These results suggest that miR-430 facilitates the deadenylation and clearance of maternal mRNAs during early embryogenesis.
Publication Title
Zebrafish MiR-430 promotes deadenylation and clearance of maternal mRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Cells located at the invasive front and in the tumor mass of mouse cervical squamous cell carcinomas were isolated by laser microdissection from hematoxylin-stained HPV/E2 sections. 7 months old HPV/E2 mice treated with oestrogen develop invasive cervical squamous cell carcinomas. This model recapitulates human invasive cervical neoplasias.
Publication Title
Inflammatory Cytokines Induce Podoplanin Expression at the Tumor Invasive Front.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 4 Downloadable Samples
IlluminaGenomeAnalyzer
Description
Proper functioning of tissues requires cells to behave in uniform, well-organized ways. Conversely, many diseases involve increased cellular heterogeneity due to genetic and epigenetic alterations. Defining the mechanisms that counteract phenotypic variability is therefore critical to understand how tissues sustain homeostasis. Here, we carried out a single-cell resolution screen of zebrafish embryonic blood vessels upon mutagenesis of single microRNA (miRNA) genes and multi-gene miRNA families. We found that miRNA mutants exhibit a profound increase in cellular phenotypic variability of specific vascular traits. Genome-wide analysis of endothelial miRNA target genes identified antagonistic regulatory nodes of vascular growth and morphogenesis signaling that allow variable cell behaviors when derepressed. Remarkably, lack of such miRNA activity greatly sensitized the vascular system to microenvironmental changes induced by pharmacological stress. We uncover a previously unrecognized role of miRNAs as a widespread protective mechanism that limits variability in cellular phenotypes. This discovery marks an important advance in our comprehension of how miRNAs function in the physiology of higher organisms. Overall design: Analysis of differential genes expression in Zebrafish endothelial cells for 4 different developmental stages
Publication Title
MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 4 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
RNAseq analysis of cloche m39 mutant zebrafish embryos and wild type siblings at 90% epiboly - tailbud stage Overall design: In order to isolate the cloche gene, RNAseq was performed on a deletion allele of the zebrafish cloche mutant. RNA was extracted from individual embryos at a stage the cloche gene was predicted to be expressed based on previous literature. RNA from the respective genoptypes was then pooled and subjected to RNAseq analysis.
Publication Title
Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
The gene expression of bone marrow cells of mice enriched for
Publication Title
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Sample Metadata Fields
Sex, Specimen part
View Samples