Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-6623
PROVIDER: PRJNA98851 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To investigate the role of FoxO transcription factors as mediators of hematopoietic stem cell resistance to oxidative stress. Keywords: Hematopoietic stem cells, myeloid progenitors, oxidative stress, ROS, Affymetrix Mouse Genome 430 2.0
2007-01-25 | GSE6623 | GEO
Project description:To investigate the role of FoxO transcription factors as mediators of hematopoietic stem cell resistance to oxidative stress. Experiment Overall Design: Study the effect of the deficiency of FoxO1, FoxO3, and FoxO4 in murine bone marrow hematopoietic stem cells and myeloid progenitors on expression of genes involved in reactive oxygen species (ROS) metabolism.
2007-11-15 | E-GEOD-6623 | biostudies-arrayexpress
Project description:Hematopoietic stem cells (HSC) activity is tightly controlled to ensure the integrity of the hematopoietic system during the organism’s lifetime. How the HSC compartment maintains its long-term fitness in condition of chronic stresses associated with systemic metabolic disorders is poorly understood. In this study, we show that obesity functionally affects the long-term function of the most immature engrafting HSC subpopulation. We link this altered regenerative activity to the oxidative stress and the aberrant constitutive activation of the AKT signaling pathway that characterized the obese environment. In contrast, we found minor disruptions of the HSC function in obese mice at steady state, suggesting that active mechanisms could protect the HSC compartment from its disturbed environment. Consistent with this idea, we found that FOXO proteins in HSCs isolated from obese mice become insensitive to their normal upstream regulators such as AKT, even during intense oxidative stress. We established that hyperglycemia, a key condition associated with obesity, is directly responsible for the alteration of the AKT-FOXO axis in HSCs and their abnormal oxidative stress response. As a consequence, we observed that HSCs isolated from a hyperglycemic environment display enhanced resistance to oxidative stress and DNA damage. Altogether, these results indicate that chronic metabolic stresses associated with obesity and/or hyperglycemia affect the wiring of the HSCs and modify their oxidative stress response. These data suggest that the uncoupling of FOXO to its environmental regulators could be a key adaptive strategy that promotes the survival of the HSC compartment in obesity.
2021-08-18 | GSE156085 | GEO
Project description:Smith2013 - Regulation of Insulin Signalling by Oxidative Stress
The model describes insulin signalling (in rodent adipocytes), which includes in addition to the core pathway, the transcriptional feedback through the Forkhead box type O (FOXO) transcription factor and interaction with oxidative stress.
This model is described in the article:
Computational modelling of the regulation of Insulin signalling by oxidative stress.
Smith GR, Shanley DP.
BMC Syst Biol. 2013 May 24;7:41.
Abstract:
BACKGROUND:
Existing models of insulin signalling focus on short term dynamics, rather than the longer term dynamics necessary to understand many physiologically relevant behaviours. We have developed a model of insulin signalling in rodent adipocytes that includes both transcriptional feedback through the Forkhead box type O (FOXO) transcription factor, and interaction with oxidative stress, in addition to the core pathway. In the model Reactive Oxygen Species are both generated endogenously and can be applied externally. They regulate signalling though inhibition of phosphatases and induction of the activity of Stress Activated Protein Kinases, which themselves modulate feedbacks to insulin signalling and FOXO.
RESULTS:
Insulin and oxidative stress combined produce a lower degree of activation of insulin signalling than insulin alone. Fasting (nutrient withdrawal) and weak oxidative stress upregulate antioxidant defences while stronger oxidative stress leads to a short term activation of insulin signalling but if prolonged can have other effects including degradation of the insulin receptor substrate (IRS1) and FOXO. At high insulin the protective effect of moderate oxidative stress may disappear.
CONCLUSION:
Our model is consistent with a wide range of experimental data, some of which is difficult to explain. Oxidative stress can have effects that are both up- and down-regulatory on insulin signalling. Our model therefore shows the complexity of the interaction between the two pathways and highlights the need for such integrated computational models to give insight into the dysregulation of insulin signalling along with more data at the individual level.A complete SBML model file can be downloaded from BIOMODELS (https://www.ebi.ac.uk/biomodels-main) with unique identifier MODEL1212210000.Other files and scripts are available as additional files with this journal article and can be downloaded from https://github.com/graham1034/Smith2012_insulin_signalling.
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2013-09-06 | BIOMD0000000474 | BioModels
Project description:Forkhead Box O (FoxO) transcription factors are conserved proteins involved in the regulation of life span and age-related diseases, such as diabetes and cancer. Stress stimuli or growth factor deprivation promote nuclear localization and activation of FoxO proteins, which - depending on the cellular context - leads to cell cycle arrest or apoptosis. Moreover, FoxOs can control oxidative stress resistance and cell metabolism. In endothelial cells (ECs), they additionally regulate angiogenesis and may promote inflammation and vessel destabilization implicating a role of FoxOs in vascular diseases. In several cancers, FoxO transcription factors exert a tumor-suppressive function, due to their critical role in regulating proliferation and survival. Others and we have previously shown that FoxOs can regulate these processes via two different mechanisms: either by direct binding to FoxO-responsive elements (FRE) at the promoter of target genes or by a poorly understood alternative process that does not require direct DNA binding and regulates key targets in primary human ECs. Here we performed an interaction study in ECs to identify new nuclear FoxO3 interaction partners, which might contribute to FoxO-dependent gene regulation. Mass spectrometry analysis of FoxO3-interacting proteins revealed Transformation/Transcription Domain-Associated Protein (TRRAP), a member of multiple histone acetyltransferase (HAT) complexes, as novel binding partner of FoxO family proteins. TRRAP is required to support FoxO3 transactivation and FoxO3-dependent apoptosis in ECs via transcriptional activation of the proapoptotic Bcl-2 family member BIM. Moreover, FoxO-TRRAP interaction might explain FoxO-induced alternative gene regulation via TRRAP-dependent recruitment to target promoters lacking FRE sequences.
2022-01-20 | PXD027615 | Pride
Project description:Maintenance of hematopoietic stem cell (HSC) function in the niche is an orchestrated event. Osteomacs (OM), are key cellular components of the niche. Previously, we documented that osteoblasts, OM, and megakaryocytes interact to promote hematopoiesis. Here, we further characterize OM and identify megakaryocyte-induced mediators that augment the role of OM in the niche. Single cell mRNAseq, mass spectrometry, and CyTOF examination of megakaryocyte-stimulated OM suggested that upregulation of CD166 and Embigin on OM augment their hematopoiesis maintenance function. CD166 knockout OM or shRNA-Embigin knockdown OM, confirmed that loss of these molecules significantly reduced OM ability to augment the osteoblast-mediated hematopoietic enhancing activity. Recombinant CD166 and Embigin partially substituted for OM function, characterizing both proteins as critical mediators of OM hematopoietic function. Our data identify Embigin and CD166 as OM-regulated critical components of HSC function in the niche and potential participants in various in vitro manipulations of stem cells.
2024-01-11 | MSV000093840 | MassIVE
Project description:isp-1;sod double mutants have decreased lifespan, increased resistance to oxidative stress and slow physiologic rates. We performed RNA sequencing to compare gene expression between isp-1 mutants and isp-1;sod-3 and isp-1;sod-5 double mutants
2017-08-30 | GSE95240 | GEO
Project description:Small nucleolar RNAs (snoRNAs) guide nucleotide modifications of cellular RNAs in the nucleus. We have previously shown that box C/D snoRNAs from the Rpl13a locus are unexpected mediators of physiologic oxidative stress, independent of their predicted ribosomal RNA modifications. Here, we demonstrate that oxidative stress induced by doxorubicin causes rapid cytoplasmic accumulation of the Rpl13a snoRNAs through a mechanism that requires superoxide and a nuclear splice variant of NADPH oxidase. RNA-sequencing analysis reveals that box C/D snoRNAs as a class are present in the cytoplasm, where their levels are dynamically regulated by NADPH oxidase. These findings suggest that snoRNAs may orchestrate the response to environmental stress through molecular interactions outside of the nucleus.
2015-03-20 | GSE67050 | GEO
Project description:G0 marker-separation of dormant and active hematopoietic stem cells reveals dormancy regulation by basal cytoplasmic calcium
2019-12-19 | PXD012093 | JPOST Repository
Project description:Recent revelations into microRNA function suggest that microRNAs serve as a key player in a robust adaptive response against stress in animals through their fine-tuning capability in gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene mir-60 in the nematode C. elegans promotes adaptive response against oxidative stress; animals lacking mir-60 dramatically extend lifespan under a mild and long-term oxidative stress condition, while they do not increase resistance against a strong and transient oxidative stress exposure. We found that canonical stress responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in the xenobiotic metabolism and pathogen defense response are up-regulated by the mir-60 loss. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis.
2016-09-27 | GSE83239 | GEO