Bitter taste receptors (T2Rs) are typical G-protein coupled receptors expressed in various tissue where they are involved in the regulation of physiological processes, thus suggesting a wider function in sensing microenvironment. We analyzed their expression and role in acute myeloid leukemia (AML). AML cells express functional T2Rs and their stimulation with the agonist, denatonium benzoate, substantially modified the AML cell transcriptomic profile and functions. GEP analysis identified relevant cellular processes affected by denatonium treatment in AML, including cell cycle, survival, migration and metabolism. More precisely, T2R activation reduced proliferation by inducing cell cycle arrest in G0/G1 phase or induced apoptosis via caspase cascade activation; impaired AML cell motility and migratory capacity; inhibited cellular respiration by decreasing glucose uptake and oxidative phosphorylation.
Denatonium as a Bitter Taste Receptor Agonist Modifies Transcriptomic Profile and Functions of Acute Myeloid Leukemia Cells.
Specimen part, Cell line, Treatment
View SamplesImmortalized, amelanotic melanocytes isolted from skin of Balb/c express enzymatically-inactive tyrosinase due to a homozygous point mutation (TGT->TCT) in tyrosinase gene, resulting in a lack of melanin . To serve as a control cell line, pigmentation was restored in these cells by correcting the point mutation using an RNA-DNA oligonucleotide (kingly gift from Dr. Alexeev Y. Vitali).
Melanocyte-secreted fibromodulin promotes an angiogenic microenvironment.
Specimen part
View SamplesSickle cell disease is characterized by hemolysis, vaso-occlusion and ischemia reperfusion injury. These events cause endothelial dysfunction and vasculopathies in multiple systems
Global gene expression profiling of endothelium exposed to heme reveals an organ-specific induction of cytoprotective enzymes in sickle cell disease.
Specimen part, Treatment
View SamplesComparative analysis of RUNX1 and RUNX2 responsiveness in the presence or absence of E2
RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.
Cell line, Treatment
View SamplesEffect of RUNX1 depletion in the presence or absence of Estradiol
RUNX1 prevents oestrogen-mediated AXIN1 suppression and β-catenin activation in ER-positive breast cancer.
Cell line, Treatment
View SamplesRhoB null mice show decreases in pathological angiogenesis in the ischemic retina and reduces angiogenesis in response to cutaneous wounding, but enhances lymphangiogenesis following both dermal wounding and inflammatory challenge.
RhoB controls coordination of adult angiogenesis and lymphangiogenesis following injury by regulating VEZF1-mediated transcription.
Sex, Specimen part
View SamplesOdorants are thought to activate sets of odorant receptors in vivo, but capturing sets of responsive receptors in vivo has never been accomplished.
In vivo identification of eugenol-responsive and muscone-responsive mouse odorant receptors.
Specimen part
View SamplesEsophageal carcinoma is the third most common gastrointestinal malignancy worldwide and is generally unresponsive to therapy. African Americans have an increased risk for esophageal squamous cell cancer (ESCC), the subtype that shows marked variation in geographic frequency. To identify key genes involved in ESC carcinogenesis in African Americans we conducted microarray expression profiling and found a significant dysregulation of genes encoding stress response and drug-metabolizing enzymes, mainly in NRF2 pathway. The involvement of NRF2 mediated oxidative damage represent a key step in the evolution of African American ESCC. Loss of activity of these enzymes would confer increased sensitivity of esophageal cells to xenobiotics, such as alcohol and tobacco smoke, and may account for the high incidence of ESCC in this ethnic group. The differential expression profile also indicates an inflammatory component and tissue regeneration in ESCC tumorigenesis. Together, these findings suggest a remarkable interplay of genetic and environmental factors in the pathogenesis of African American ESCC.
African-American esophageal squamous cell carcinoma expression profile reveals dysregulation of stress response and detox networks.
Race
View SamplesThis study demonstrates simulated microgravity effects on E. coli K 12 MG1655 when grown on LB medium supplemented with glycerol. The results imply that E. coli readily reprograms itself to combat the multiple stresses imposed due to microgravity. Under these conditions it survives by upregulating oxidative stress protecting genes and simultaneously down regulating the membrane transporters and synthases to maintain cell homeostasis.
Effect of simulated microgravity on E. coli K12 MG1655 growth and gene expression.
No sample metadata fields
View SamplesRegulation of RNA levels is critical for the response to external stimuli and determined through the interplay between RNA production, processing and degradation. Despite the centrality of these processes, most global studies of RNA regulation do not distinguish their separate contributions and relatively little is known about how they are temporally integrated. Here, we combine metabolic labeling of RNA with advanced RNA quantification assays and computational modeling to estimate RNA transcription and degradation during the response of immune dendritic cells (DCs) to pathogens, a critical and tightly regulated step in innate immunity. We find that transcription regulation plays a major role in shaping most temporal changes in RNA levels, but that changes in degradation rate are important for shaping sharp ‘peaked’ responses. We find that transcription changes precede corresponding RNA changes by a small lag (15-30 min), which is shorter for induced than for repressed genes. Massively parallel sequencing of the entire RNA population – including non-polyadenylated transcripts – allows us to estimate RNA processing, and identify specific groups of transcripts, mostly cytokines and transcription factors, undergoing enhanced mRNA maturation. This suggests an additional role for splicing in regulating mRNA maturation. Our method provides a new quantitative approach to study key steps in the integrative process of RNA regulation. Overall design: Sequencing of 4sU-labeled RNA taken from a 7 samples time-series (one sample every 1 hour) during the response of DCs to LPS stimulation. 4-thiouridine was added 45 minutes prior to sample collection. Data presented here for six timepoints: 0, 1, 3-6 hrs. 2hr timepoint not included.
Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cells.
No sample metadata fields
View Samples