We have analyzed the variation of transcriptome of HUVECs intoxicated by the lethal toxin of Bacillus anthracis at 4 and 8 hours
Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity.
Specimen part
View SamplesNeurons exploit mRNA localization and local translation to spatio-temporally regulate gene expression during development. Local translation and retrograde transport of transcription factors regulate nuclear gene expression in response to signaling events at distal neuronal ends. Whether epigenetic factors could also be involved in such regulation is not known. We report that the mRNA encoding the high mobility group N5 (HMGN5) chromatin binding protein localizes to growth cones of both neuronal-like cells and of hippocampal neurons. We show that Hmgn5 3UTR drives growth cone localization and translation of a reporter gene, and that HMGN5 can be retrogradely transported into the nucleus along neurites. Loss of HMGN5 function induces transcriptional changes and impairs neurite outgrowth while HMGN5 overexpression induces neurite outgrowth and global chromatin decompaction. Interestingly, control of both neurite outgrowth and chromatin structure is dependent on proper growth cone localization of Hmgn5 mRNA. Our results provide the first evidence that mRNA localization and local translation might serve as a mechanism to couple the dynamic neuronal outgrowth process with chromatin regulation in the nucleus.
Growth Cone Localization of the mRNA Encoding the Chromatin Regulator HMGN5 Modulates Neurite Outgrowth.
No sample metadata fields
View SamplesObjectives: Long non-coding RNAs (lncRNAs) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of esophageal adenocarcinoma (EAC) and its progression. Design: lncRNAs that are abnormally upregulated in EACs were identified by RNA-seq analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 31 EAC patients. Cell biological assays in combination with siRNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. Results: We discovered that a lncRNA, HNF1A-AS1, is markedly upregulated in human primary EACs relative to their corresponding normal esophageal tissues (mean fold change 7.2, p<0.01). We further discovered that HNF1A-AS1 knockdown significantly inhibited cell proliferation and anchorage independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p<0.05). A gene ontological analysis revealed that HNF1A-AS1 knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well-known cancer-related lncRNA, H19, was the gene most markedly inhibited by HNF1A-AS1 knockdown. Consistent to this finding, there was a significant positive correlation between HNF1A-AS1 and H19 expression in primary EACs (p<0.01). Overall design: In order to identify novel oncogenic lncRNAs in esophageal adenocarcinogenesis, we carried out RNA-seq of a matched NE-BE-EAC tissue pair
Long non-coding RNA HNF1A-AS1 regulates proliferation and migration in oesophageal adenocarcinoma cells.
Specimen part, Disease, Disease stage, Subject
View SamplesWe have previously identified hundreds of human islet lncRNAs. Here we functionally characterise 12 such lncRNAs in EndoC-betaH1 cells through loss of function studies.
Human Pancreatic β Cell lncRNAs Control Cell-Specific Regulatory Networks.
Cell line
View SamplesTwo major subsets of rat natural killer (NK) cells can be distinguished based on their expression of either the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors.
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines.
Specimen part
View SamplesDiabetes and obesity are widespread diseases with signifciant socioeconomic implications. We used three different types of human adipose tissue (epigastric, visceral, and subcutaneous) in order to determine differences in global gene expression between these adipose depots in severely obese patients.
Gene expression profiling in subcutaneous, visceral and epigastric adipose tissues of patients with extreme obesity.
Specimen part, Race
View SamplesOxidative DNA damage has been associated with cognitive decline. The Ogg1 and Mutyh DNA glycosylases cooperate to prevent mutations caused by 8-oxoG, a major premutagenic oxidative DNA base lesion. Here, we have examined behavior and cognitive function in mice deficient of these glycosylases. We found that Ogg1-/-Mutyh-/- mice were more active and less anxious and that their learning ability was impaired. In contrast, Mutyh-/- mice showed moderately improved memory compared to WT. There was no change in genomic 8-oxoG levels, suggesting that Ogg1 and Mutyh play minor roles in global repair in adult brain. Notably, transcriptome analysis of hippocampus revealed that differentially expressed genes in the mutant mice belong to pathways known to be involved in anxiety and cognitive function. Thus, beyond their involvement in DNA repair, Ogg1 and Mutyh modulate cognitive function and behavior, and related hippocampal gene expression, suggesting a novel role for 8-oxoG in regulating adaptive behavior. Overall design: The mRNA profiles from hippocampus of WT, Ogg1-/-, Mutyh-/- and Ogg1-/- Mutyh-/- C57BL/6 mice at 6month of age were generated by RNA sequencing using Illumina Hiseq 2000
Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice.
Age, Specimen part, Cell line, Subject
View SamplesBarretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease, Subject
View SamplesBarretts esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Transplantation of transformed Barretts stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease
View SamplesBarretts esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barretts have been stymied by our inability to identify the Barretts stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barretts, gastric, and esophageal epithelium. Genomic analyses of Barretts stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barretts stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barretts develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.
Mutational spectrum of Barrett's stem cells suggests paths to initiation of a precancerous lesion.
Specimen part, Disease, Disease stage
View Samples