Oxygen Level Modulates Mitochondria Mass and Pluripotent Marker Expression in Induced Pluripotent Stem Cells Through Sirtuin 1
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE120148 | GEO | 2021/01/04
REPOSITORIES: GEO
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Project description:Oxygen Level Modulates Mitochondria Mass and Pluripotent Marker Expression in Induced Pluripotent Stem Cells Through Sirtuin 1
| PRJNA491733 | ENA
Project description:We studied how Fusobacterium nucleatum infection under hypoxia regulated the epigenome and transcriptome of colon cancer cells. The six datasets that are described in this study are labeled as follows: (a) Normoxia - No Bacteria (NN), (b) Normoxia - infection with Fnn (NF), (c) Normoxia - infection with E. coli (NE), (d) Hypoxia - No Bacteria (HN), (e) Hypoxia - infection with Fnn (HF), and (f) Hypoxia - infection with E. coli (HE).
2024-02-07 | GSE246615 | GEO
Project description:We studied how Fusobacterium nucleatum infection under hypoxia regulated the epigenome and transcriptome of colon cancer cells. The six datasets that are described in this study are labeled as follows: (a) Normoxia - No Bacteria (NN), (b) Normoxia - infection with Fnn (NF), (c) Normoxia - infection with E. coli (NE), (d) Hypoxia - No Bacteria (HN), (e) Hypoxia - infection with Fnn (HF), and (f) Hypoxia - infection with E. coli (HE).
2024-02-07 | GSE246614 | GEO
Project description:To simulate in vitro different oxidative stress exposures, AC16 cells were cultured either under physioxia (5% oxygen) or normoxia (21% oxygen), and were consequently harvested either under physioxia or normoxia.
2021-09-10 | PXD023620 | Pride
Project description:Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease. Total RNA were isolated from HESC, HF(Pompe disease), PomD-iPSC, HES-CMLC, and PomD-iPS-CMLC. The series included two HESC lines, two HF(Pompe disease) cell lines, four PomD-iPS cell lines, and HES-CMLC were differentiated from one HESC line(HESC2), PomD-iPS-CMLC were differentiated from 3 PomD-iPS cell lines(PomD-iPSC A10, PomD-iPSC A17, PomD-iPSC B03). Each condition was repeated twice and used HESC as control.
2011-02-17 | E-GEOD-27280 | biostudies-arrayexpress
Project description:Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
2011-02-17 | GSE27280 | GEO
Project description:Sirtuins are a highly conserved family of proteins whose activity can prolong the lifespan of model organisms such as yeast, worms and flies. Mammals contain seven sirtuins (SIRT1-7) that modulate distinct metabolic and stress response pathways. Three sirtuins, SIRT3, SIRT4 and SIRT5, are located in the mitochondria, dynamic organelles that function as the primary site of oxidative metabolism and play crucial roles in apoptosis and intracellular signaling. Recent findings have shed light on how the mitochondrial sirtuins function in the control of basic mitochondrial biology, including energy production, metabolism, apoptosis and intracellular signaling.
| S-EPMC2992946 | biostudies-literature
Project description:Reactive oxygen species (ROS) are by-products of physiological mitochondrial metabolism that are involved in several cellular signaling pathways as well as tissue injury and pathophysiological processes, including brain ischemia/reperfusion injury. The mitochondrial respiratory chain is considered a major source of ROS; however, there is little agreement on how ROS release depends on oxygen concentration. The rate of H2 O2 release by intact brain mitochondria was measured with an Amplex UltraRed assay using a high-resolution respirometer (Oroboros) equipped with a fluorescent optical module and a system of controlled gas flow for varying the oxygen concentration. Three types of substrates were used: malate and pyruvate, succinate and glutamate, succinate alone or glycerol 3-phosphate. For the first time we determined that, with any substrate used in the absence of inhibitors, H2 O2 release by respiring brain mitochondria is linearly dependent on the oxygen concentration. We found that the highest rate of H2 O2 release occurs in conditions of reverse electron transfer when mitochondria oxidize succinate or glycerol 3-phosphate. H2 O2 production by complex III is significant only in the presence of antimycin A and, in this case, the oxygen dependence manifested mixed (linear and hyperbolic) kinetics. We also demonstrated that complex II in brain mitochondria could contribute to ROS generation even in the absence of its substrate succinate when the quinone pool is reduced by glycerol 3-phosphate. Our results underscore the critical importance of reverse electron transfer in the brain, where a significant amount of succinate can be accumulated during ischemia providing a backflow of electrons to complex I at the early stages of reperfusion. Our study also demonstrates that ROS generation in brain mitochondria is lower under hypoxic conditions than in normoxia. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
| S-EPMC7086484 | biostudies-literature
Project description:O-GlcNAcylation is a reversible post-translational modification involved in the regulation of cytosolic, nuclear, and mitochondrial proteins. Only two enzymes, OGT (O-GlcNAc transferase) and OGA (O-GlcNAcase), control the attachment and removal of O-GlcNAc on proteins, respectively. Whereas a variant OGT (mOGT) has been proposed as the main isoform that O-GlcNAcylates proteins in mitochondria, identification of a mitochondrial OGA has not been performed yet. Two splice variants of OGA (short and long isoforms) have been described previously. In this work, using cell fractionation experiments, we show that short-OGA is preferentially recovered in mitochondria-enriched fractions from HEK-293T cells and RAW 264.7 cells, as well as mouse embryonic fibroblasts. Moreover, fluorescent microscopy imaging confirmed that GFP-tagged short-OGA is addressed to mitochondria. In addition, using a Bioluminescence Resonance Energy Transfer (BRET)-based mitochondrial O-GlcNAcylation biosensor, we show that co-transfection of short-OGA markedly reduced O-GlcNAcylation of the biosensor, whereas long-OGA had no significant effect. Finally, using genetically encoded or chemical fluorescent mitochondrial probes, we show that short-OGA overexpression increases mitochondrial ROS levels, whereas long-OGA has no significant effect. Together, our work reveals that the short-OGA isoform is targeted to the mitochondria where it regulates ROS homoeostasis.
| S-EPMC9180253 | biostudies-literature
Project description:Induced pluripotent stem cells (iPSCs) hold promise for generating personalized xenogenic organs via development of cross-species chimeric animals. However, whether human and other primate iPSCs are capable of establishing cross-species chimeras remains unknown. Recognizing the ethical concerns of cross-species chimerism using human iPSCs, we explored the capacity for cross-species chimerism between distinct, non-human primates. Injection of either pig-tailed macaque iPSCs or chimpanzee iPSCs into the rhesus macaque blastocyst embryos demonstrated that these cells survive, proliferate, and integrate near the rhesus inner cell mass (ICM). Ectopic expression of BCL2 in pig-tailed and chimpanzee iPSCs greatly improved the success rate of establishing cross-species blastocyst chimerism. This study represents the first successful cross-species blastocyst chimerism between distinct, non-human primate species, and highlights critical factors that may be necessary to unlock the broad potential of primate iPSCs to form cross-species chimeras, with diverse applications for basic research and translational medicine.
2020-09-30 | GSE155443 | GEO