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GSE47196
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cholecystokinin (CCK) is a satiety hormone produced by discrete enteroendocrine cells scattered among absorptive cells of the small intestine. CCK is released into blood following a meal; however, the mechanisms inducing hormone secretion are largely unknown. Ingested fat is the major stimulant of CCK secretion. We recently identified a novel member of the lipoprotein remnant receptor family known as immunoglobulin-like domain containing receptor 1 (ILDR1) in intestinal CCK cells and postulated that this receptor conveyed the signal for fat-stimulated CCK secretion. In the intestine, ILDR1 is expressed exclusively in CCK cells. Orogastric administration of fatty acids elevated blood levels of CCK in wild type but not ILDR1-deficient mice, although the CCK secretory response to trypsin inhibitor was retained. The uptake of fluorescently labeled lipoproteins in ILDR1-transfected CHO cells and release of CCK from isolated intestinal cells required a unique combination of fatty acid plus HDL. CCK secretion secondary to ILDR1 activation is associated with increased [Ca2+]i consistent with regulated hormone release. These findings demonstrate that ILDR1 regulates CCK release through a mechanism dependent on fatty acids and lipoproteins and that absorbed fatty acids regulate gastrointestinal hormone secretion.
Publication Title
Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
The canonical Wnt signaling pathway is critical for myogenesis and can induce muscle progenitors to switch from proliferation to differentiation; how Wnt signals integrate with muscle specific regulatory factors in this process is poorly understood. We previously demonstrated that the Barx2 homeobox protein promotes differentiation in cooperation with the muscle regulatory factor (MRF) MyoD. Pax7, another important muscle homeobox factor represses differentiation. We now identify Barx2,MyoD,and Pax7 as novel components of the Wnt effector complex, providing a new molecular pathway for regulation of muscle progenitor differentiation. Canonical Wnt signaling induces Barx2 expression in muscle progenitors and perturbation of Barx2 leads to misregulation of Wnt target genes. Barx2 activates two endogenous Wnt target promoters as well as the Wnt reporter gene TOPflash, the latter synergistically with MyoD. Moreover, Barx2 interacts with the core Wnt effectors ß-catenin and TCF, is recruited to TCF/LEF sites, and promotes recruitment of ß-catenin. In contrast, Pax7 represses the Wnt reporter gene and antagonizes the activating effect of Barx2. Pax7 also binds ß-catenin suggesting that Barx2 and Pax7 may compete for interaction with the core Wnt effector complex. Overall, the data show for the first time that Barx2, Pax7, and MRFs can act as direct transcriptional effectors of Wnt signals in myoblasts and that Barx2 and Wnt signaling participate in a regulatory loop. We propose that antagonism between Barx2 and Pax7 in regulation of Wnt signaling may help mediate the switch from myoblast proliferation to differentiation. Overall design: RNA-Seq analyses was used to characterize gene expression in primary myoblasts from wild-type and Barx2 knockout mice.
Publication Title
Barx2 and Pax7 have antagonistic functions in regulation of wnt signaling and satellite cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Estrogen-related receptor ? (ERR?) signaling increases during the neonatal to adult transition in pancreatic islet ß-cells. We show that ß-cell-specific ERR?-deficient (ßERR?KO) mice exhibit glucose intolerance with reduced glucose-stimulated insulin secretion (GSIS) and ßERR?KO islets have defective GSIS function accompanied by changes in genes that regulate ATP biosynthesis, oxidative phosphorylation, and the electron transport chain. ERR? overexpression enhances genes involved in mitochondrial metabolism, resulting in transformation of ß-like-cells into metabolically functional ß-cells that can ameliorate STZ-induced hyperglycemia in NOD-SCID mice. These results suggest that ERR? signaling is essential for the metabolic maturation of ß-like-cells and thus represents a novel therapeutic target in the treatment of diabetes.
Publication Title
ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
We characterized the effect of loss of ERR expression in mouse pancreatic islets using adenoviral constructs.
Publication Title
ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaHiSeq2500
Description
We show that ERR? overexpression in ß-like-cells differentiated from human iPSCs enhances genes involved in mitochondrial metabolism, resulting in transformation of these cells into metabolically functional ß-cells that can ameliorate STZ-induced hyperglycemia in NOD-SCID mice. These results suggest that ERR? signaling is essential for the metabolic maturation of ß-like-cells and thus represents a novel therapeutic target in the treatment of diabetes.
Publication Title
ERRγ Is Required for the Metabolic Maturation of Therapeutically Functional Glucose-Responsive β Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Neurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERR) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERR directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERR, and reduced long-term potentiation (LTP) in ERR-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERR knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERR exhibit defects in spatial learning and memory. These findings implicate ERR in the metabolic adaptations required for long-term memory formation.
Publication Title
Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We report the expression profiles of the nuclear receptor family of transcription factors, known regulators of metabolism, during iPSC generation. Unique but overlapping expression patterns were found in iPSCs derived from adipose derived stem cells (ADSCs) and embryonic fibroblasts (human and mouse) that correlate with developmental transitions in the cell.
Publication Title
ERRs Mediate a Metabolic Switch Required for Somatic Cell Reprogramming to Pluripotency.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed RNA sequencing analysis of hepatic gene expression a few hours after amlexanox treatment, and identified over 1700 differentially expressed genes. Pathway analysis of these differentially regulated genes revealed that the top two most enriched pathways were the adipocytokine signaling pathway and the Jak-STAT signaling pathway. Overall design: RNA-seq analysis of hepatic gene expression was used to identify differentially expressed genes in response to Amlexanox treatment.
Publication Title
A subcutaneous adipose tissue-liver signalling axis controls hepatic gluconeogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The circadian system regulates numerous physiological processes including the adaptive immune system. Here we show that mice deficient for the circadian genes Cry1 and Cry2, (DKO) display an autoimmune phenotype including higher serum IgG concentration, presence of serum anti-nuclear antibodies, precipitation of IgG, IgM and complement 3 in glomeruli, and massive infiltrations of leukocytes into the lung and kidney. Activation of Cry DKO splenic B cells elicited markedly enhanced and prolonged tyrosine phosphorylation of cellular proteins compared to cells from control mice, suggesting that over activation of the BCR signaling pathway may contribute to autoimmunity in the Cry DKO mice. Expression of C1q, deficiency of which contributes to the pathogenesis of Systemic lupus erythematosus (SLE), was significantly downregulated in Cry DKO B cells. This suggests that B cell development, BCR signaling pathway and C1q expression may be under direct circadian control and dysregulation of which contributes to autoimmunity.
Publication Title
Circadian clock cryptochrome proteins regulate autoimmunity.
Sample Metadata Fields
Specimen part
View Samples