Liver X Receptors (LXRa and ß) are ligand-activated transcription factors that play a key role in the control of lipid homeostasis, as well as modulation of immunity and inflammation. Besides ligand binding, LXR activity can be regulated by posttranslational modifications, such as phosphorylation. This study aims to assess changes in bone marrow derived macrophage transcriptional profiles of mice that carry LysMcre directed phosphorylation deficient-version of LXRa compared (S196A) to wild-type (WT). Overall design: BMDM mRNA profiles of either LdlrKO or M-LXRa-S196A-LdlrKO male mice after being fed a Western diet for 12 weeks. 12 samples, 4 groups, in triplicate: (1) LdlrKO basal, (2) LdlrKO+ ligand, (3) M-LXRa-S196A-LdlrKO basal, (4) M-LXRa-S196A-LdlrKO+ligand
Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation.
Specimen part, Cell line, Subject
View SamplesFetal mice (16 days gestation) were administered feline immunodeficiency virus (FIV)-based lentiviral viral particles containing the gene encoding GFP. Six liver tumors developed in three mice between the ages of 273 and 484 days, each mouse developed 2 tumors. These tumors and non-tumorous liver tissue from the same animals and animals that did not develop tumors and untransduced controls were harvested and microarrays were performed on total RNA extracted from these samples. We were interested in investigating the link between lentiviral integration and gene expression.
Transduction of fetal mice with a feline lentiviral vector induces liver tumors which exhibit an E2F activation signature.
Sex, Age, Specimen part
View SamplesWe describe here an interrupted reprogramming strategy to generate "induced Progenitor-Like (iPL) cells" from Alveolar Epithelial Type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4 and c-Myc; OSKM) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state.
Interrupted reprogramming of alveolar type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis.
Specimen part
View SamplesExpression data from Sheep longissimus dorsi (LD) muscle during development; fetal lambs (80, 100, 120 days gestation), new born lambs at birth (150 d) and lambs at 12 weeks (230 d)
A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development.
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View SamplesPulmonary Hypertension (PH) is a frequent complication of Pulmonary Fibrosis (PF). PH can be seen in PF in the abscence of hypoxemia, irrespective of the degree of fibrosis. At the same time, a consistent number of patients with advanced PF never develop PH. The pathogenesis of PH secondary to PF remains unclear. PF patients are often referred to lung transplantation, but they present a higher incidence of pimary graft dysfunction than other diseases. The cause of this is unknown, and the relationship with PH remains unclear.
Gene expression profiling in the lungs of patients with pulmonary hypertension associated with pulmonary fibrosis.
Specimen part, Disease, Disease stage
View SamplesThe C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors. Overall design: Ikaros RNA-Seq from double positive thymocytes comparing wt (n=2), Ikaros-ZnF1-/- mutant (n=2) and Ikaros-ZnF4-/- mutant (n=2)
Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.
Sex, Age, Specimen part, Cell line, Subject
View SamplesThe C2H2 zinc finger is the most prevalent DNA-binding motif in the mammalian proteome, with DNA-binding domains usually containing more tandem fingers than are needed for stable sequence-specific DNA recognition. To examine the reason for the frequent presence of multiple zinc fingers, we generated mice lacking finger 1 or finger 4 of the 4-finger DNA-binding domain of Ikaros, a critical regulator of lymphopoiesis and leukemogenesis. Each mutant strain exhibited a specific subset of the phenotypes observed with Ikaros null mice. Of particular relevance, fingers 1 and 4 contributed to distinct stages of B- and T-cell development and finger 4 was selectively required for tumor suppression in thymocytes and in a new model of BCR-ABL+ acute lymphoblastic leukemia. These results, combined with transcriptome profiling (this GEO submission: RNA-Seg of whole thymus from wt and the two ZnF mutants), reveal that different subsets of fingers within multi-finger transcription factors can regulate distinct target genes and biological functions, and they demonstrate that selective mutagenesis can facilitate efforts to elucidate the functions and mechanisms of action of this prevalent class of factors. Overall design: RNA-Seq from sorted primary proB cell Hardy Fractions B and C+C'', comparing wt, Ikaros-ZnF1-/- mutant and Ikaros-ZnF4-/- mutant.
Selective regulation of lymphopoiesis and leukemogenesis by individual zinc fingers of Ikaros.
Specimen part, Cell line, Subject
View SamplesAlthough multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH.
De novo synthesize of bile acids in pulmonary arterial hypertension lung.
Specimen part
View SamplesThe expression was designed to determine whether exposure to CSF1-Fc has any effect on liver-specific gene expression in pigs.
Macrophage colony-stimulating factor (CSF1) controls monocyte production and maturation and the steady-state size of the liver in pigs.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis.
Specimen part, Time
View Samples