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Mus musculus
12 Downloadable Samples
Illumina HiSeq 2000
Description
MicroRNAs (miRNA) are small, non-coding RNAs mediating post-transcriptional regulation of gene expression. miRNAs have recently been implicated in hippocampus-dependent functions such as learning and memory, although the roles of individual miRNAs in these processes remain largely unknown. Here, we achieved stable inhibition using AAV-delivered miRNA sponges of individual, highly expressed and brain-enriched miRNAs; miR-124, miR-9 and miR-34, in hippocampal neurons. Molecular and cognitive studies revealed a role for miR-124 in learning and memory. Inhibition of miR-124 resulted in an enhanced spatial learning and working memory capacity, potentially through altered levels of genes linked to synaptic plasticity and neuronal transmission. In contrast, inhibition of miR-9 or miR-34 led to a decreased capacity of spatial learning and of reference memory, respectively. On a molecular level, miR-9 inhibition resulted in altered expression of genes related to cell adhesion, endocytosis and cell death, while miR-34 inhibition caused transcriptome changes linked to neuroactive ligand-receptor transduction and cell communication. In summary, this study establishes distinct roles for individual miRNAs in hippocampal function. Overall design: Three RNA samples containing bilateral entire hippocampi from three different mice, per group. Group 1 were injected with vector containing GFP and a miR34sp/miR9sp and the other group were subjected to a vector expressing GFP only.
Publication Title
Distinct cognitive effects and underlying transcriptome changes upon inhibition of individual miRNAs in hippocampal neurons.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We established a neuron-specific Argonaute2:GFP-RNA immunoprecipitation followed by high throughput sequencing (AGO2-RIP-seq) to analyse the regulatory role of miRNAs in mouse hippocampal neurons. Using this technique, we identified more than two thousand miRNA target genes in hippocampal neurons, regulating essential neuronal features such as axon guidance and transcription. Furthermore, we found that stable inhibition of the highly expressed miR-124 in hippocampal neurons led to significant changes in the AGO2 binding of target mRNAs, resulting in subsequent upregulation of numerous miRNA target genes. Our data suggest that target redundancies are common among microRNA families. Together, these findings greatly enhance our understanding of the mechanisms and dynamics through which miRNAs regulate their target genes in neurons. Overall design: Analysis of the miRNA targetome in hippocampal neurons after inhibition of 2 different miRNAs. AAV5 injections into the hippocampus of adult C57BL/6 mice producing either of the following under a synapsin promoter: GFP only (Samples beginning with ''GFP124…'' or ''GFP125…''), GFP-miR124sp (Samples beginning with ''miR124…''), GFP-miR125sp (Samples beginning with ''miR125…''), GFP-AGO2-miR292sponge (samples ending with ''…292''), GFP-AGO2-miR124sponge (samples ending with ''…124''), GFP-AGO2-miR125sponge (samples ending with ''…125''). All other samples were sham-injected.
Publication Title
Identification of the miRNA targetome in hippocampal neurons using RIP-seq.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Affymetric arrays were performed on thyroid samples collected from GEMMs: normal thyroid, TPO-Cre/LSL-Braf (PTC), TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (ATC) and TPO-Cre/tetO-BRAF/LSL-rtTAiresGFP/p53-flox (recurrent tumors)
Publication Title
Hgf/Met activation mediates resistance to BRAF inhibition in murine anaplastic thyroid cancers.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
BACKGROUND. Poorly-differentiated (PDTC) and anaplastic (ATC) thyroid cancers are rare and frequently lethal tumors, which so far have not been subjected to comprehensive genetic characterization. METHODS. We performed next generation sequencing of 341 cancer genes in 117 PDTCs and ATCs, and a transcriptomic analysis of a representative subset of 37 tumors. Results were analyzed in the context of The Cancer Genome Atlas (TCGA) study of papillary thyroid cancers (PTC). RESULTS. ATCs have a greater mutation burden than PDTCs, and higher mutation frequency of TP53, TERT promoter, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits and histone methyltransferases. BRAF and RAS are the predominant drivers, and dictate remarkably distinct tropism for nodal vs. distant metastases in PDTC. RAS and BRAF sharply distinguish between PDTCs defined by the Turin (PDTC-Turin) vs. MSKCC (PDTC-MSK) criteria, respectively. Mutations of EIF1AX, a component of the translational preinitiation complex, are markedly enriched in PDTCs and ATCs, and have a striking pattern of co-occurrence with RAS. TERT promoter mutations are rare and subclonal in PTCs, whereas they are clonal and highly prevalent in advanced cancers. Application of the TCGA-derived BRAF-RAS score (a measure of MAPK transcriptional output) shows a preserved relationship with BRAF/RAS mutation in PDTCs, whereas ATCs are BRAF-like irrespective of driver mutation. CONCLUSIONS. These data support a model of tumorigenesis whereby PDTCs and ATCs arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities, many of which have prognostic and possible therapeutic relevance. The widespread genomic disruptions in ATC compared to PDTC underscore their greater virulence and higher mortality.
Publication Title
Genomic and transcriptomic hallmarks of poorly differentiated and anaplastic thyroid cancers.
Sample Metadata Fields
Sex, Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Purpose: To identify genes that are transcriptionally controlled by Notch signaling during zebrafish lateral line proneuromast formation. Methods: We isolated primordium cells from dissected tails of 36 hpf Tg((cldnB:GFP);Tg(cldnB:gal4) x Tg(UAS:nicd)) and sibling Tg((cldnB:GFP);Tg(cldnB:gal4)) embryos by FACS and performed RNASeq analysis. Results: Using an optimized data analysis workflow, we mapped about 26 million sequence reads per sample to the zebrafish genome (build danRer10) and identified 32,105 transcripts in the dissociated tails of WT and NICD zebrafish with TopHat workflow. Approximately 2% of the transcripts showed differential expression between the WT and NICD tails, with a fold change =0.5 and p value <0.01. Conclusion: RNASeq analyses revealed that Notch signaling cell-autonomously induces apical constriction and cell adhesion. Overall design: Zebrafish lateral line mRNA profiles of 36 hours wild type (WT) and NICD embryos were generated in triplicate, using HiSeq 2500 (Illumina).
Publication Title
Proliferation-independent regulation of organ size by Fgf/Notch signaling.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The Hippo pathway effectors yes-associated protein (YAP) and WW domain containing transcription regulator 1 (TAZ/WWTR1) support tumor initiation and progression in various cancer entities including hepatocellular carcinoma (HCC). However, to which extent YAP and TAZ contribute to liver tumorigenesis via common and exclusive molecular mechanisms is poorly understood. RNAinterference (RNAi) experiments illustrate that YAP and TAZ individually support HCC cell viability and migration, while for invasion additive effects were observed. Comprehensive expression profiling revealed partly overlapping YAP/TAZ target genes as well as exclusively regulated genes.
Publication Title
TAZ target gene ITGAV regulates invasion and feeds back positively on YAP and TAZ in liver cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Class IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis, we used siRNA to specifically suppress the individual HDAC isoenzymes. Among the HDAC isoforms tested, silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The anti-angiogenic activity of HDAC5 was independent of MEF2 binding and its deacetylase activity, but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. ChIP assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, like FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The de-repression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis.
Publication Title
HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- NextSeq 550
Description
RNA seqeuncing was performed to identifiy changes in genes expression and alternative splicing following SRSF3 depletion in pluripotent stem cells. Overall design: Induced pluripotent stem cells (iPSCs) generated from reprogrammable conditional SRSF3 knockout (SRSF3-KO/OKSM) mouse embryonic fibroblasts (MEFs) were induced for 24h to deplete SRSF3 and RNA seqeuncing was performed.
Publication Title
SRSF3 promotes pluripotency through <i>Nanog</i> mRNA export and coordination of the pluripotency gene expression program.
Sample Metadata Fields
Specimen part, Subject
View Samples
GSE107033- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Impaired or excessive growth of endothelial cells contributes to several diseases. However, the functional involvement of regulatory long non-coding RNAs in these processes is not well defined. Here we show that the long non-coding antisense transcript of GATA6 (GATA6-AS) interacts with the epigenetic regulator LOXL2 to regulates endothelial gene expression via changes in histone methylation. Using RNA deep sequencing, we find that GATA6-AS is up-regulated in endothelial cells during hypoxia. Silencing of GATA6-AS diminishes TGF-2-induced endothelial-mesenchymal transition in vitro and promotes formation of blood vessels in mice. We identify LOXL2, known to remove activating H3K4me3 chromatin marks, as a GATA6-AS-associated protein, and reveal a set of angiogenesis-related genes that are inversely regulated by LOXL2 and GATA6-AS silencing. As GATA6-AS silencing reduces H3K4me3 methylation of two of these genes, periostin and cyclooxygenase-2, we conclude that GATA6-AS acts as negative regulator of nuclear LOXL2 function.
Publication Title
The lncRNA GATA6-AS epigenetically regulates endothelial gene expression via interaction with LOXL2.
Sample Metadata Fields
No sample metadata fields
View Samples