This SuperSeries is composed of the SubSeries listed below.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
Specimen part
View SamplesLong non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development. Overall design: Time course RNA-Seq analysis H1 ESCs differentiated into endothelial cells
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
No sample metadata fields
View SamplesLong non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression and chromatin modifications, with important functions in development and disease. Here we sought to identify and functionally characterize lncRNAs critical for vascular vertebrate development with significant conservation across species. Genome-wide transcriptomic analyses during human vascular lineage specification enabled the identification of three conserved novel lncRNAs: TERMINATOR, ALIEN and PUNISHER that are specifically expressed in pluripotent stem cells, mesoderm and endothelial cells, respectively. Gene expression profiling, alongside RNA immunoprecipitation coupled to mass spectrometry, revealed a wide range of new molecular networks and protein interactors related to post-transcriptional modifications for all three lncRNAs. Functional experiments in zebrafish and murine embryos, as well as differentiating human cells, confirmed a developmental-stage specific role for each lncRNA during vertebrate development. The identification and functional characterization of these three novel non-coding provide a comprehensive transcriptomic roadmap and shed new light on the molecular mechanisms underlying human vascular development.
Identification of novel long noncoding RNAs underlying vertebrate cardiovascular development.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Specimen part, Cell line, Treatment
View SamplesTo identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Specimen part, Cell line, Treatment
View SamplesCortical tubers in patients with tuberous sclerosis complex (TSC) are associated with cognitive disability and intractable epilepsy. While these developmental malformations are believed to result from the effects of TSC1 or TSC2 Gene mutations, the molecular mechanisms leading to tuber formation during brain development as well as the onset of seizures remain largely unknown. We used the Affymetrix Gene Chip platform as a genome-wide strategy to define the Gene expression profile of cortical tubers resected during epilepsy surgery compared to histologically normal perituberal tissue (adjacent to the cortical tuber) from the same patients or autopsy control tissue.
Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors.
Specimen part, Disease, Subject
View SamplesGene expression signatures were measured in logarithmic growing cultures
Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF.
Specimen part
View SamplesThe ADAR RNA editing enzymes deaminate adenosine bases to inosines in cellular RNAs, recoding open reading frames. Human ADAR1 mutations cause Aicardi-Goutieres Syndrome (AGS) and Adar1 mutant mice showing an aberrant interferon response and death by embryonic day E12.5 model the human disease. Searches have not identified key ADAR1 RNA editing sites recoding immune/haematopoietic proteins but editing is widespread in Alu sequences. We show that Adar1 embryonic lethality is rescued in Adar1; Mavs double mutant mice in which general antiviral responses to cytoplasmic dsRNA are prevented. We propose that inosine bases are epigenetic marks identifying cellular RNA as innate immune ÒselfÓ. Consistent with this idea we show that an editing-active cytoplasmic ADAR is required to prevent aberrant immune responses in Adar1 mutant mouse embryo fibroblasts. No dramatic increase in repetitive transcripts is observed. AGS mutations in ADAR1 affect editing by the interferon-inducible cytoplasmic ADAR1 isoform. Overall design: RNA-seq expression profiling in Adar1 and Adar1/Mavs knockout mice embryos.
The RNA-editing enzyme ADAR1 controls innate immune responses to RNA.
No sample metadata fields
View SamplesSeed dormancy is the inability for seeds to germinate even under favorable conditions. In the Arabidopsis Landsberg <i>erecta</i> (L<i>er</i>) ecotype, 2 weeks of dry storage, called after-ripening, is sufficient to relieve seed dormancy. Such seed is referred to as after-ripened (AR) and has a high rate of germination when imbibed. While widespread transcriptome changes have been previously observed with seed dormancy loss, this experiment was designed to characterize transcriptional changes associated with the increased seed dormancy and dormancy loss of the gibberellin (GA) hormone-insensitive <i>sleepy1-2</i> (<i>sly1-2</i>) mutant. The <i>SLY1</i> gene encodes the F-box subunit of an SCF E3 ubiquitin ligase needed for GA-triggered proteolysis of DELLA repressors of seed germination. In the <i>sly1-2</i> mutant, GA-directed DELLA proteolysis cannot occur leading to DELLA protein accumulation and increased dormancy. <i>sly1-2</i> mutant seeds are fully dormant at 2 weeks of dry storage (0% germination), but germinate well with very long after-ripening (51% germination after 19 months). <i>sly1-2</i> seed germination can also be rescued by overexpression of the GA receptor, <i>GA-INSENSITIVE DWARF1b</i> (<i>GID1b-OE</i>), which resulted in 74% germination at 2 weeks of dry storage. In this experiment, we compared seeds of wild-type L<i>er</i> at 2 weeks of dry storage (non-dormant), dormant <i>sly1-2</i> (2 weeks of dry storage; <i>sly1-2</i>(D)), long after-ripened <i>sly1-2</i> (non-dormant, 19 months of dry storage; <i>sly1-2</i>(AR)), and <i>sly1-2 GID1b-OE</i> (non-dormant, 2 weeks of dry storage). Samples were collected at two imbibition timepoints: 1) a 0h timepoint after 4 days at 4°C, and 2) a 12h timepoint after 4 days at 4°C followed by 12 hours in the light at 22°C. These timepoints were selected to capture the transcriptomes at an early and late time in Phase II of imbibition. Using this experimental design we were able to determine transcriptome differences associated with seed dormancy in the <i>sly1-2</i> mutation (L<i>er</i> wt vs <i>sly1-2</i>(D)), and changes associated with <i>sly1-2</i> dormancy loss through dry after-ripening (<i>sly1-2</i>(AR) vs <i>sly1-2</i>(D)) or through <i>GID1b</i>-overexpression (<i>sly1-2 GID1b-OE</i> vs <i>sly1-2</i>(D)). Seeds for L<i>er</i> wt, <i>sly1-2</i>(D), and <i>sly1-2 GID1b-OE</i> were grown alongside each other under the same conditions and after-ripened for 2 weeks. Seeds from <i>sly1-2</i>(AR) were grown under the same conditions in advance of the other lines to allow for the long after-ripening requirement. RNA was extracted using a phenol-chloroform-based extraction from three biological replicates per treatment.
Transcriptional mechanisms associated with seed dormancy and dormancy loss in the gibberellin-insensitive sly1-2 mutant of Arabidopsis thaliana.
Specimen part, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Regulation of epithelial-mesenchymal transition in breast cancer cells by cell contact and adhesion.
Specimen part, Cell line
View Samples