Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA407300 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Inositol Trisphosphate Receptor Mediated Ca2+ Signalling Stimulates Mitochondrial Function and Gene Expression in Core Myopathy Patients [Human arrays]
| PRJNA407301 | ENA
Project description:Inositol Trisphosphate Receptor Mediated Ca2+ Signalling Stimulates Mitochondrial Function and Gene Expression in Core Myopathy Patients
| PRJNA407299 | ENA
Project description:Elevated inositol trisphosphate receptor (IP3R) levels have been previously reported in skeletal muscle myotubes derived from patients with ryanodine receptor 1 (RyR1) mutation related core myopathies. However, the functional relevance and the relationship of IP3R mediated Ca2+ signalling with the pathophysiology of the disease is unclear. It has also been suggested that mitochondrial dysfunction underlies the development of central and diffuse multi-mini-cores, devoid of mitochondrial activity, a key pathological consequence of RyR1 mutations. Here we used muscle biopsies of central core and multi-minicore disease patients with RyR1 mutations, as well as cellular and in vivo mouse models of the disease to characterise whole genome and mitochondrial gene expression to assess if remodeling of skeletal muscle following loss of functional RyR1 mediates bioenergetic adaptation.
2020-09-15 | GSE103854 | GEO
Project description:Elevated inositol trisphosphate receptor (IP3R) levels have been previously reported in skeletal muscle myotubes derived from patients with ryanodine receptor 1 (RyR1) mutation related core myopathies. However, the functional relevance and the relationship of IP3R mediated Ca2+ signalling with the pathophysiology of the disease is unclear. It has also been suggested that mitochondrial dysfunction underlies the development of central and diffuse multi-mini-cores, devoid of mitochondrial activity, a key pathological consequence of RyR1 mutations. Here we used muscle biopsies of central core and multi-minicore disease patients with RyR1 mutations, as well as cellular and in vivo mouse models of the disease to characterise whole genome and mitochondrial gene expression to assess if remodeling of skeletal muscle following loss of functional RyR1 mediates bioenergetic adaptation.
2020-09-15 | GSE103853 | GEO
Project description:Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a molecule enriched in the brain and neurons that regulates intracellular calcium levels via signaling through the inositol trisphosphate receptor. In the present study, we found that IP3K-A expression is highly enriched in the central nucleus of the amygdala (CeA), which plays a pivotal role in the processing and expression of emotional phenotypes in mammals. We used microarray to identify differentially expressed genes in the amydala of wild type (WT) and IP3K-A KO mice.
2016-01-21 | GSE77001 | GEO
Project description:Transcriptional regulation in the absence of inositol trisphosphate receptor signaling
| PRJNA1193071 | ENA
Project description:During graft-versus-host disease (GVHD), Ca2+ signals are crucial for the establishment of T cell alloim-munity, however, excessive or prolonged Ca2+ signals lead to T cell death and dysfunction. How alloreac-tive T cells regulate a delicate regulate intracellular Ca2+ response to induce GVHD remains poorly defined. We demonstrate that Ezh2 acts as Ca2+ signaling brake to limit excessive intracellular Ca2+ responses in activated T cells, thereby promoting survival of alloreactive T cells that mediate GVHD. Ezh2 loss resulted in enhanced intracellular Ca2+ responses and upregulation of gene programs that promote effector differen-tiation in activated T cells. Conditional deletion of Stim1 (which mediates cytosolic Ca2+ entry) synthetical-ly rescued antigen-activated non-viable Ezh2-null T cells and their capacity to induce GVHD. Ezh2 re-pressed the expression of endoplasmic reticulum Ca2+ release channel inositol 1,4,5-trisphosphate (InsP3) receptor 2 (Itpr2) to modulate intracellular Ca2+ responses. Deleting Itpr2 in Ezh2-null T cells reduced cy-tosolic Ca2+ entry, improved their capacity to mediate GVHD and eliminate leukemia in mice. Our findings identify that Ezh2 is a master regulator of Ca2+ signals in antigen-driven T cells. Furthermore, selectively heightening intracellular Ca2+ signals in alloreactive T cells may lead to new strategies to control GVHD.
2026-07-08 | GSE275046 | GEO
Project description:During graft-versus-host disease (GVHD), Ca2+ signals are crucial for the establishment of T cell alloim-munity, however, excessive or prolonged Ca2+ signals lead to T cell death and dysfunction. How alloreac-tive T cells regulate a delicate regulate intracellular Ca2+ response to induce GVHD remains poorly defined. We demonstrate that Ezh2 acts as Ca2+ signaling brake to limit excessive intracellular Ca2+ responses in activated T cells, thereby promoting survival of alloreactive T cells that mediate GVHD. Ezh2 loss resulted in enhanced intracellular Ca2+ responses and upregulation of gene programs that promote effector differen-tiation in activated T cells. Conditional deletion of Stim1 (which mediates cytosolic Ca2+ entry) synthetical-ly rescued antigen-activated non-viable Ezh2-null T cells and their capacity to induce GVHD. Ezh2 re-pressed the expression of endoplasmic reticulum Ca2+ release channel inositol 1,4,5-trisphosphate (InsP3) receptor 2 (Itpr2) to modulate intracellular Ca2+ responses. Deleting Itpr2 in Ezh2-null T cells reduced cy-tosolic Ca2+ entry, improved their capacity to mediate GVHD and eliminate leukemia in mice. Our findings identify that Ezh2 is a master regulator of Ca2+ signals in antigen-driven T cells. Furthermore, selectively heightening intracellular Ca2+ signals in alloreactive T cells may lead to new strategies to control GVHD.
2026-07-08 | GSE275045 | GEO
Project description:Mutations in inositol trisphosphate receptor type 3 (ITPR3) have been linked to immunodeficiency, including an expansion of effector memory (EM) CD4+ T cells within peripheral tissues. We developed a mouse model that genocopied a single allelic (p.R2524C) ITPR3 mutation found in humans.
2026-05-21 | GSE332595 | GEO
Project description:Nutrient cues shape adipose homeostasis; however, the mechanism by which inorganic signals engage organelle networks to drive white fat browning remains unclear. Here, we identify a nitrate-Sialin2 pathway that converts dietary nitrate into a spatially confined thermogenic program. Sialin2 localizes to mitochondria and endoplasmic reticulum (ER) to strengthen ER-mitochondria contacts and engage the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1)-voltage-dependent anion channel 1 (VDAC1)-mitochondrial calcium uniporter 1 (MCU1) conduit, boosting inducible mitochondrial Ca2+ uptake. In parallel, Sialin2 associates with lysosomal acid lipase (LIPA), Acyl-CoA Synthetase Long Chain Family Member 3 (ACSL3), and carnitine palmitoyltransferase 1A (CPT1A) to direct lipid-droplet-derived fatty acids into β-oxidation, thereby fueling the tricarboxylic acid (TCA) cycle and uncoupling protein 1 (UCP1)-dependent respiration. Loss of Slc17a5 abolishes nitrate-evoked browning and metabolic benefits, whereas nitrate supplementation improves adipose thermogenesis and systemic indices in diet-induced obesity without adrenergic stimulation. These findings reveal an organelle-specific nitrate-sensing mechanism that couples ionic signaling with substrate routing to reprogram adipocytes, providing a non-hormonal strategy for restoring metabolic homeostasis.
2026-05-17 | MTBLS14192 | MetaboLights