Fumarate hydratase (FH) mutations predispose to renal cysts cancer. These cancers overexpress hypoxia-inducible factor-alpha (Hif-1a). We have generated a conditional Fh1 (mouse FH) knockout mice that develop renal cysts and overexpress Hif-1a. In order to identify the contribution of Hif-1a to cyst formation we have intercrossed our mice with conditional HIf-1a KO mice.
Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Specimen part, Disease
View SamplesMicroarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. It has been applied to yeast and other systems but not to blood samples.
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
Specimen part, Disease
View SamplesMicroarray deconvolution is a technique for quantifying the relative abundance of constituent cells in a mixture based on that mixture's microarray signature and the signatures of the purified constituents. Its ability to discriminate related human cells is unknown.
Deconvolution of blood microarray data identifies cellular activation patterns in systemic lupus erythematosus.
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View SamplesFamilial hypertrophic cardiomyopathy (FHC) is a disease characterized by ventricular hypertrophy, fibrosis, and aberrant systolic and/or diastolic function. Our laboratories have previously developed 2 mouse models that affect cardiac performance. One transgenic mouse model encodes an FHC-associated mutation in -tropomyosin (Tm180) that displays severe cardiac hypertrophy with fibrosis and impaired physiological performance. The other model was a gene knockout of phospholamban (PLB), a regulator of calcium uptake in the sarcoplasmic reticulum of cardiomyocytes; the hearts of these mice exhibit hypercontractility with no pathological abnormalities. Previous work in our laboratories show that the hearts of mice that were genetically crossed between the Tm180 and PLB KO mice rescues the hypertrophic phenotype and improves their cardiac morphology and function.
Microarray analysis of active cardiac remodeling genes in a familial hypertrophic cardiomyopathy mouse model rescued by a phospholamban knockout.
Age, Specimen part
View SamplesTranscript data from heart tissue from fasted-state male BXD strains on chow or high fat diet
Quantifying and Localizing the Mitochondrial Proteome Across Five Tissues in A Mouse Population.
Specimen part, Treatment
View SamplesTranscript data from livers from fasted-state BXD strains on chow or high fat diet
Multilayered genetic and omics dissection of mitochondrial activity in a mouse reference population.
Specimen part
View SamplesTo gain insight into the role of Runx3 in TrkC neurons we performed RNA-seq on E11.5 TrkC neurons isolated from cervical ganglia of Runx3-P2+/- and Runx3-P2-/- mice Overall design: Runx3-P2 mice express GFP in TrkC neurons enabling the FACS isolation of TrkC neurons from E11.5 embryos, Heterozygote Runx3-P2+/-(n=pool of 4) and homozygote Runx3-P2-/- (n=pool of 4) TrkC/GFP neurons were isolated,
An ensemble of regulatory elements controls Runx3 spatiotemporal expression in subsets of dorsal root ganglia proprioceptive neurons.
Specimen part, Cell line, Subject
View SamplesBackground: Ion channels are key determinants for the function of excitable cells but little is known about their role and involvement during cardiac development. Earlier work identified Ca2+-activated potassium channels of small and intermediate conductance (SKCas) as important regulators of neural stem cell fate. Here, we have investigated their impact on the differentiation of pluripotent cells towards the cardiac lineage. Methods and Results: We have applied the SKCa-activator EBIO on embryonic stem cells and identified this particular ion channel family as a new critical target involved in the generation of cardiac pacemaker-like cells: SKCa-activation led to rapid remodeling of the actin cytoskeleton, inhibition of proliferation, induction of differentiation and diminished teratoma formation. Time-restricted SKCa-activation induced cardiac mesoderm and commitment to the cardiac lineage as shown by gene regulation, protein and functional electrophysiological studies. In addition, the differentiation into cardiomyocytes was modulated in a qualitative fashion, resulting in a strong enrichment of pacemaker-like cells. This was accompanied by induction of the sino-atrial gene program and in parallel by a loss of the chamber-specific myocardium. In addition, SKCa activity induced activation of the Ras-Mek-Erk signaling cascade, a signaling pathway involved in the EBIO-induced effects.
Modulation of calcium-activated potassium channels induces cardiogenesis of pluripotent stem cells and enrichment of pacemaker-like cells.
Specimen part, Cell line
View SamplesPeripheral blood mononuclear cells were collected from SLE patients in an observational study performed at the University of Michigan
Association of the interferon signature metric with serological disease manifestations but not global activity scores in multiple cohorts of patients with SLE.
Disease
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