Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sex, Age, Specimen part
View SamplesCharacterization of the underlying genetic defects in patients with a rare and peculiar phenotype is challenging. Here we have utilized whole genome expression profiling, and identified a homozygous germline mutation in the DDB2 gene in a patient with several facial tumors. The feasibility of using blood derived RNA, diminishing costs of the technology, and the limited number of samples needed provide this approach a powerful new tool that may substantially aid in such gene identification efforts.
Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease.
No sample metadata fields
View SamplesEffect of fumarase point mutation or knock-out on transcriptional profile in yeast to model hereditary leiomyomatosis and renal cell cancer (HLRCC).
Modeling tumor predisposing FH mutations in yeast: effects on fumarase activity, growth phenotype and gene expression profile.
Sex, Subject
View SamplesThe intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals. Overall design: Intestinal mRNA profiles of 7 days old mated females of UAS-mCD8::GFP, hsFLP; tub-GAL4/+; FRT82B tub-GAL80/FRT82B genotype kept in calorie-restriction +/- 0.1M D-acetylglucosamine for 24h.
Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content.
Sex, Specimen part, Treatment, Subject
View SamplesSerrated adenocarcinomas are morphologically different from conventional adenocarcinomas. The serrated pathway has recently been proposed to represent a novel mechanism of colorectal cancer (CRC) formation. However, whether they are biologically different and truly form a distinct subclass of CRC, is not known. This study shows that the gene expression profile of serrated and conventional CRCs differs from each others and that serrated CRCs are not only morphologically novel, but also biologically distinct subclass of CRC.
Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis.
No sample metadata fields
View SamplesWhile identification of genes mutated in high penetrance tumor predisposition syndromes has been a success story, much less progress has been made in characterizing the genetic basis of low penetrance tumor susceptibility. Combining recently introduced chip-based technologies with traditional genealogy work we have identified inactivating germline mutations in patients with pituitary adenoma predisposition (PAP).
Pituitary adenoma predisposition caused by germline mutations in the AIP gene.
No sample metadata fields
View SamplesHeart disease and failure is a leading cause of mortality worldwide. Left ventricular hypertrophy (LVH) and myocardial fibrosis are the major risk factor for cardiovascular morbidity and mortality and the development of heart failure. Pathological LVH induced by sustained pressure-overload engages transcriptional programs including reactivation of canonical fetal genes and those inducing fibrosis. Histone lysine demethylases (KDMs) are emerging potent regulators of transcriptional reprogramming in cancer, though their potential role in abnormal growth and fibrosis in heart disease remains little understood. Here, we investigated gain and loss of function of an H3K9me2 specific demethylase, Kdm3a, in myocytes and in vivo, and show it promotes LVH and myocardial fibrosis in response to pressure-overload. Cardiomyocyte KDM3A activates the transcription of tissue-inhibitor of MMP type 1 (Timp1) with pro-fibrotic activity. By contrast, a pan-KDM inhibitor, JIB-04, suppresses TAC-induced LVH and fibrosis. JIB-04 inhibits KDM3A and suppresses the transcription of fibrotic genes that overlap with genes downregulated in Kdm3a-KO mice versus WT controls. Our study provides genetic and biochemical evidence for a pro-hypertrophic function of KDM3A and proof-of principle for pharmacological targeting of KDMs as an effective strategy to counter LVH and pathological fibrosis.
Histone lysine dimethyl-demethylase KDM3A controls pathological cardiac hypertrophy and fibrosis.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View SamplesSystems vaccinology has emerged as an interdisciplinary field that combines systems wide measurements and network and predictive modeling applied to vaccinology.
Systems biology of vaccination for seasonal influenza in humans.
Specimen part, Subject, Time
View Samples