Gene expression changes in Itpr triple conditional knockout T cell progenitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE57997 | GEO | 2014/05/28
SECONDARY ACCESSION(S): PRJNA248666
REPOSITORIES: GEO
Similar Datasets
Project description:Calicum plays critical roles in developing T cells, promoting survival, proliferation, and differentiation at multiple stages of maturation. Calcium release from intracellular stores due to T cell receptor and pre-T cell receptor signaling is thought to require the inositol triphosphate receptors (Itpr), however the requirement for these receptors has not been investigated. We used microarrays to examine gene expression differences between control and Itpr deficient T cell progenitors. We used microarrays to identify changes in the transcriptional programme of developing T cells prior to acquisition of a mature T cell receptor and identified several developmentally important genes altered in the absence of Itpr. Thymocyte progenitors at DN4 or ISP were harvested for RNA extraction from three independent control Itpr1/Itpr2/Itpr3 triple homozygous floxed (CTL) or Tie2-Cre Itpr1/Itpr2/Itrp3 triple homozygous floxed (KO) thymii, pooled, and hybridized on Affymetrix microarrarys. To obtain a homogenous population of thymocyte progenitors, we FACS purified cells and collect RNA from only DN4 or ISP T cells. ISP T cells were defined as CD4- CD8+ CD24+ CD3-. DN4 T cells were defined as CD45+ CD24+ CD3- CD4- CD8- CD25- CD44- CD19- B220- gdTCR- Ter119- Mac1- Gr1-. Thymocytes were harvested from neonatal mice, ranging from 7 to 10 days of age and lacked any signs of malignancy or disease.
2014-05-28 | E-GEOD-57997 | biostudies-arrayexpress
Project description:Vesicular traffic and membrane contact sites between organelles enable the exchange of proteins, lipids, and metabolites. Recruitment of membrane tethers to contact sites between the endoplasmic reticulum (ER) and the plasma membrane is often triggered by calcium. In contrast, we reveal here a function for calcium in the repression of cholesterol export at membrane contact sites between the ER and the Golgi complex. We show that calcium efflux from ER stores induced by inositol-triphosphate [IP3] accumulation upon loss of the inositol 5-phosphatase INPP5A or sustained receptor signaling triggers the depletion of cholesterol and associated complex glycosphingolipids from the cell surface, resulting in a blockade of clathrin-independent endocytosis (CIE) of bacterial Shiga toxin. This phenotype is caused by the calcium-induced dissociation of oxysterol binding protein (OSBP) from the Golgi complex and from VAP-containing membrane contact sites. Our findings reveal a crucial function for INPP5A-mediated IP3 hydrolysis in the control of lipid exchange at membrane contact sites.
2021-05-06 | MTBLS2444 | MetaboLights
Project description:This pilot, randomized phase I/II trial studies how well inositol works in preventing colorectal cancer in patients with abnormal cells (dysplasia) associated with inflammation of the colon (colitis). Patients with colitis-associated dysplasia may have an increased risk of developing colorectal cancer. Inositol is a vitamin-like substance that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
| 2088185 | ecrin-mdr-crc
Project description:This a model from the article:
Metabotropic receptor activation, desensitization and sequestration-I: modelling
calcium and inositol 1,4,5-trisphosphate dynamics following receptor activation.
Lemon G, Gibson WG, Bennett MR. J Theor Biol
2003 Jul 7;223(1):93-111 12782119
,
Abstract:
A mathematical account is given of the processes governing the time courses of
calcium ions (Ca2+), inositol 1,4,5-trisphosphate (IP(3)) and
phosphatidylinositol 4,5-bisphosphate (PIP(2)) in single cells following the
application of external agonist to metabotropic receptors. A model is
constructed that incorporates the regulation of metabotropic receptor activity,
the G-protein cascade and the Ca2+ dynamics in the cytosol. It is subsequently
used to reproduce observations on the extent of desensitization and
sequestration of the P(2)Y(2) receptor following its activation by uridine
triphosphate (UTP). The theory predicts the dependence on agonist concentration
of the change in the number of receptors in the membrane as well as the time
course of disappearance of receptors from the plasmalemma, upon exposure to
agonist. In addition, the extent of activation and desensitization of the
receptor, using the calcium transients in cells initiated by exposure to
agonist, is also predicted. Model predictions show the significance of membrane
PIP(2) depletion and resupply on the time course of IP(3) and Ca2+ levels.
Results of the modelling also reveal the importance of receptor recycling and
PIP(2) resupply for maintaining Ca2+ and IP(3) levels during sustained
application of agonist.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Lemon G, Gibson WG, Bennett MR. (2003) - version=1.0
The original CellML model was created by:
Wei Liu
wliu052@aucklanduni.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230039 | BioModels
Project description:Background: Cysteinyl leukotrienes (cysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through cysteinyl leukotriene receptors may influence the migration and activity of cells such as eosinophils, monocytes and dendritic cells. Objective: To determine the gene expression signature of human monocytes in response to cysLTs and to elucidate the signaling pathways involved in monocyte activation. Methods: Gene expression was analyzed using oligonucleotide microarrays. Responsiveness to cysLTs was assessed by real-time PCR, calcium flux, kinase activation and chemotaxis assays. Results: Cysteinyl leukotriene type I receptor (CysLTR1) transcript 1 is predominantly expressed in human monocytes and cysLTs signal through CysLTR1 in these cells. Several immediate-early genes, including early growth response (Egr) -2, 3, FosB, activating transcription factor 3 and nuclear receptor subfamily 4 were significantly induced by LTD4. This effect was mediated by CysLTR1 coupled to Gαi/o, activation of phospholipase C, and inositol-1,4,5-triphosphate (IP3) and store operated calcium channels. LTD4 induced p38 MAP kinase phosphorylation, a pathway also involved in the regulation of immediate-early genes expression in monocytes. LTD4 stimulated monocyte chemotactic activity that was fully blocked by a selective CysLTR1 inhibitor MK571 and pertussis toxin, suggesting that CysLTR1 coupled to Gαi/o is a dominant functional pathway in human monocytes. Conclusion: Our data show that cysLTs acting through CysLTR1 can significantly influence the activation and migration of human monocytes and that these effects can be fully inhibited by CysLTR1 antagonists. Clinical implications: Antileukotriene therapies are likely to significantly block the proinflammatory functions of human monocytes. Experiment Overall Design: 4 control sample, 4 LTD4 stimulated samples
2008-06-15 | E-GEOD-7807 | biostudies-arrayexpress
Project description:The Stromal interaction molecule 1 (STIM1) is an ER-Ca2+ sensor and an essential component of ER-Ca2+ store operated Ca2+entry (SOCE). Loss of STIM1 affects metabotropic Glutamate Receptor 1 (mGluR1) mediated synaptic transmission, neuronal Ca2+ homeostasis and intrinsic plasticity in Purkinje Neurons (PNs). Long-term changes of intracellular Ca2+ signaling in PNs lead to neurodegenerative conditions, as evident in individuals with mutations of the ER-Ca2+ channel, the Inositol, 1,4,5-triphosphate receptor (IP3R). Moreover, Changes in gene expression upon reduced SOCE in non-excitable immune cells, the developing mouse brain, Drosophila pupal neurons and human neural precursor cells have been reported. Gene expression profiles of mature differentiated neurons with loss of STIM1/nSOC have not been published to date. The study evaluated the differential gene expression in STIM1 knockout purkinje neurons compared to wild type purkinje neurons from 1 year old mice. Analysis of gene expression profiles demonstrated that STIM1 dependent Ca2+ homeostasis and signaling helps to maintain the expression of multiple key components of synaptic architecture and function in ageing animals. Our findings are significant in the context of finding new therapeutic means of alleviating the neurodegenerative changes associated with human SCAs.
2021-03-22 | GSE158513 | GEO
Project description:In differentiated skeletal muscle, intracellular Ca2+ concentrations rise dramatically upon membrane depolarization, constituting the link between excitation and contraction (EC). Transient rises in [Ca2+]i mainly emerge from Ca2+ released by the type 1 ryanodine receptor (RYR1) and, in non-adult muscle, by the inositol 1,4,5-triphosphate receptor (IP3R) of the sarcoplasmic reticulum (SR), the dominant Ca2+ store in skeletal muscle. While the IP3R-mediated, slow Ca2+ transients, have been implicated in cell signaling and development, RYR1’s non-contractile role(s) remain obscure. We used a homozygous mouse RyR1 knockout model (dyspedic) to investigate the effects of the absence of a functional RYR1 and, consequently, the lack of RyR1-mediated Ca2+ signaling during embryogenesis. While heterozygous mice of the model are undistinguishable from WT littermates, homozygous dyspedic mice die at birth from asphyxia, since their skeletal muscle does not support EC coupling. Furthermore, they display abnormal spine curvature, subcutaneous hematomas, small limbs, and enlarged neck. Skeletal muscles from front and hind limbs of dyspedic embryos (day E18.5) were subjected to microarray analyses, revealing 318 genes, significantly regulated by at least 50 % compared to control heterozygous littermates.
2016-02-01 | E-MTAB-3608 | biostudies-arrayexpress
Project description:Background: Cysteinyl leukotrienes (cysLTs) are important mediators of innate immune responsiveness and chronic inflammatory diseases. CysLTs acting through cysteinyl leukotriene receptors may influence the migration and activity of cells such as eosinophils, monocytes and dendritic cells. Objective: To determine the gene expression signature of human monocytes in response to cysLTs and to elucidate the signaling pathways involved in monocyte activation. Methods: Gene expression was analyzed using oligonucleotide microarrays. Responsiveness to cysLTs was assessed by real-time PCR, calcium flux, kinase activation and chemotaxis assays. Results: Cysteinyl leukotriene type I receptor (CysLTR1) transcript 1 is predominantly expressed in human monocytes and cysLTs signal through CysLTR1 in these cells. Several immediate-early genes, including early growth response (Egr) -2, 3, FosB, activating transcription factor 3 and nuclear receptor subfamily 4 were significantly induced by LTD4. This effect was mediated by CysLTR1 coupled to Gαi/o, activation of phospholipase C, and inositol-1,4,5-triphosphate (IP3) and store operated calcium channels. LTD4 induced p38 MAP kinase phosphorylation, a pathway also involved in the regulation of immediate-early genes expression in monocytes. LTD4 stimulated monocyte chemotactic activity that was fully blocked by a selective CysLTR1 inhibitor MK571 and pertussis toxin, suggesting that CysLTR1 coupled to Gαi/o is a dominant functional pathway in human monocytes. Conclusion: Our data show that cysLTs acting through CysLTR1 can significantly influence the activation and migration of human monocytes and that these effects can be fully inhibited by CysLTR1 antagonists. Clinical implications: Antileukotriene therapies are likely to significantly block the proinflammatory functions of human monocytes. Keywords: monocytes stimulated with LTD4
2007-08-30 | GSE7807 | GEO
Project description:Intracellular signaling is conserved in eukaryotes to allow for response to extracellular signals and to regulate development and cellular functions. In fungi, inositol phosphate signaling has been shown to be involved in growth, sexual reproduction, and metabolic adaptation lacking, however, reports of mushroom forming fungi so far. In Schizophyllum commune, an inositol monophosphatase has been found up-regulated during sexual development. The enzyme is crucial for inositol cycling where it catalyzes the last step of inositol phosphate metabolism restoring the inositol pool from the monophosphorylated inositol monophosphate. We overexpressed the gene in this model basidiomycete and verified its involvement in cell wall integrity and intracellular trafficking. Strong phenotypes in mushroom formation and cell metabolism were evidenced by proteome analyses. In addition, altered inositol signaling was shown to be involved in tolerance towards cesium and zinc, and increased metal tolerance towards cadmium, associated with induced expression of kinases and repression of phosphatases within the inositol cycle. The presence of the heavy metals Sr, Cs, Cd, and Zn lowered intracellular calcium levels. We could develop a model integrating inositol signaling in the known signal transduction pathways governed by Ras, G-protein coupled receptors, cAMP and elucidate different roles in development.
2021-07-01 | PXD026465 | Pride
Project description:A collection of four induced pluripotent stem cell models (iPSC) derived from patients diagnosed with Spinocerebellar ataxia 15 (SCA15) . Spinocerebellar ataxia 15 (SCA15) is a neurological condition characterised by progressive gait and limb ataxia as well as abnormalities in eye movement and difficulties with balance, speech and swallowing (Synofzik et al., 2011). Whole Genome Sequencing was performed to confirm the presence of a heterozygous deletions in the inositol 1,4,5-triphosphate receptor gene (ITPR1), characteristic of the disease. Cell models names: HPSI0216i-vieg_5 or Vieg_5 (WTSIi472-A), HPSI0216i-vieg_3 or Vieg_3 (WTSIi472-B), HPSI0216i-dacv_6 or Dacv_6 (WTSIi554-A), HPSI0216i-boho_3 or Boho_3 (WTSIi502-A). All iPSC models are available via ECACC-Culture Collections.
| EGAD00001009851 | EGA