The Acute Respiratory Distress Syndrome (ARDS)/Acute Lung Injury (ALI) was described 30 years ago, yet the interaction between specific sets of genes involved in this syndrome remains incompletely understood.
Discovery of the gene signature for acute lung injury in patients with sepsis.
No sample metadata fields
View SamplesMicroarray data from this study represent the first global transcriptional survey of gene expression during early compared to late diaphragm formation.
Congenital diaphragmatic hernia candidate genes derived from embryonic transcriptomes.
No sample metadata fields
View SamplesWe report the gene expression profiles of normal epithelial and carcinoma cell populations that differ in their relative levels of integrin-beta 4 expression. ITGB4 high, mesenchymal subtype, triple-negative breast cancer cells were found to be more epithelial than related ITGB4 low cells. Overall design: RNA-seq was used to compare the expression of mesenchymal-like carcinoma cell subtypes isolated from polyclonal cell populations. Isolated cell populations that had high levels of ITGB4 were found to be more epithelial than those with low levels, despite the fact that they were within the mesenchymal-like cell state spectrum.
Integrin-β4 identifies cancer stem cell-enriched populations of partially mesenchymal carcinoma cells.
Specimen part, Cell line, Subject
View SamplesBone adaptation to mechanical loading is regulated via signal transduction by mechano-sensing osteocytes. Mineral-embedded osteocytes experience strain-induced interstitial fluid flow and fluid shear stress, and broad shifts in gene expression are key components in the signaling pathways that regulate bone turnover. RNA sequencing analysis, or RNA-Seq, enables more complete characterization of mechano-sensitive transcriptome regulation than previously possible. We hypothesized that RNA-Seq of osteocytic MLO-Y4 cells reveals both expected and novel gene transcript regulation in cells previously fluid flowed and analyzed using gene microarrays (Govey et al., J Biomech, 2014). MLO-Y4 cells were flowed for 2 h with 1 Pa oscillating fluid shear stress and post-incubated 2 h. RNA-Seq of original samples detected 58 fluid flow-regulated gene transcripts (p-corrected<0.05) versus 65 transcripts detected by microarray. However, RNA-Seq demonstrated greater dynamic range, with all 58 transcripts >1.5 fold-change whereas 10 of 65 met this cut-off by microarray. Analyses were complimentary in patterns of regulation, though only 6 transcripts were significant in both analyses: Cxcl5, Cxcl1, Zc3h12a, Ereg, Slc2a1, and Egln1. As part of a broad inflammatory response inferred by gene ontology analyses, we again observed greatest up-regulation of inflammatory C-X-C motif chemokines, and newly implicated HIF-1? and AMPK signaling pathways. Importantly, we detected both expected mechano-sensitive transcripts (e.g. Nos2, Ptgs2, Ccl7) and transcripts not previously identified as mechano-sensitive, e.g. Ccl2. We found RNA-Seq advantageous over microarrays because of its ability to analyze unbiased estimation of gene expression, informing our understanding of osteocyte signaling. Overall design: Osteocyte-like MLO-Y4 cells were subjected to 2 hours of 10 dyn/cm^2 oscillating fluid flow in parallel-plate fluid flow chambers and harvested for analysis after an additional 2 hours post-flow incubation in fresh medium. Parallel control samples from sham treated cells were also collected. Triplicate samples of both flow and non-flow control conditions were collected to analyze flow vs. non-flow gene transcript regulation.
Functional and structural characterization of osteocytic MLO-Y4 cell proteins encoded by genes differentially expressed in response to mechanical signals in vitro.
No sample metadata fields
View SamplesA time course of infection of the alphavirus Sindbis virus (SINV) was used to investigate the presence of viral specific vsRNA and the changes in miRNAs profiles in human embryonic kidney 293 cells (HEK293) by high throughput DNA sequencing. Deep sequencing of small RNAs early in SINV infection (4 and 6 hpi) showed low abundance (0.8%) of viral specific RNAs (vsRNAs) , with a random uniform distribution not typical of Dicer products, suggesting they arise from non-specific degradation. Sequencing showed little variation of cellular microRNAs (miRNAs) at 4 and 6 hpi compared to uninfected cells. Twelve miRNAs exhibiting some minor differential expression by sequencing, showed insignificant modulation by Northern blot analysis. Overall design: RNA was isolated from mock infected and SINV inoculated HEK 293 cells at 4hpi and 6hpi cDNA libraries were generated for the small RNA (sRNA) content of the cells and sequenced using Illumina GA II, which yielded between 29.1M and 30.5M reads per sample
Small RNA analysis in Sindbis virus infected human HEK293 cells.
Specimen part, Cell line, Subject
View SamplesThe CREB binding protein inhibitor ICG-001 suppresses pancreatic cancer growth
The CREB-binding protein inhibitor ICG-001 suppresses pancreatic cancer growth.
Cell line, Treatment
View SamplesMetabolic production of acetyl-CoA has been linked to histone acetylation and gene regulation, however the mechanisms are largely unknown. We show that the metabolic enzyme acetyl-CoA synthetase 2 (ACSS2) is a critical and direct regulator of histone acetylation in neurons and of long-term mammalian memory. We observe increased nuclear ACSS2 in differentiating neurons in vitro. Genome-wide, ACSS2 binding corresponds with increased histone acetylation and gene expression of key neuronal genes. These data indicate that ACSS2 functions as a chromatin-bound co-activator to increase local concentrations of acetyl-CoA and to locally promote histone acetylation for transcription of neuron-specific genes. Remarkably, in vivo attenuation of hippocampal ACSS2 expression in adult mice impairs long-term spatial memory, a cognitive process reliant on histone acetylation. ACSS2 reduction in hippocampus also leads to a defect in upregulation of key neuronal genes involved in memory. These results reveal a unique connection between cellular metabolism and neural plasticity, and establish a link between generation of acetyl-CoA and neuronal chromatin regulation. Overall design: Global survey of gene expression in CAD cells and differentiated CAD neurons following lentiviral knockdown of ACSS2 or ATP citrate lyase (ACL) (and control = scramble hairpin); survey of hippocampal gene expression changes associated with retrieval of fear memory, after ACSS2-AAV knockdown or in EGFP-AAV control (comparison of 0h vs. 1h post-memory retrieval).
Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory.
Specimen part, Cell line, Treatment, Subject, Time
View SamplesIn this study, time dependent genome wide lung mRNA profiling changes were assessed using C57BL/6J and A/J mice. Through comprehensive bioinformatics and functional genomics analyses, we identified both temporal and strain dependent gene expression patterns, systemically mapped key regulators, bioprocesses, and transcriptional networks controlling lung maturation, providing the basis for new therapeutic strategies to enhance lung function in preterm infants.
Transcriptional programs controlling perinatal lung maturation.
Specimen part, Time
View SamplesThere are an estimated 21million diabetics in the United States and 150 million diabetics worldwide. The World Health Organization anticipates that these numbers will double in the next 20 years. Metabolic syndrome is a well recognized set of symptoms that increases a patients risk of developing diabetes. Insulin resistance is a factor in both metabolic syndrome and Type 2 diabetes. It is characterized by decreased insulin stimulated glucose uptake in peripheral tissues, decreased adiponectin levels, increased adipocyte FFA and cytokine production, and increased insulin and hepatic glucose output. Prevention or reversal of insulin resistance should serve as an important strategy in addressing the growing health concerns posed by the Diabetes epidemic. While increased adiposity is associated with insulin resistance, the role of the cell types present within adipose (adipocytes, pre-adipocytes, endothelial cells, macrophages, fibroblasts, leukocytes and smooth muscle cells) in insulin resistance is unclear. In an effort to begin dissection of this question, we examined the transcriptional response of the buoyant and non-buoyant fractions isolated from insulin sensitive or TNF induced insulin resistant hMSC derived adipocytes before and after treatment with insulin.
Genome-wide profiling of H3K56 acetylation and transcription factor binding sites in human adipocytes.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative survival-based molecular profiling of human pancreatic cancer.
Specimen part, Disease, Disease stage
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