Caballano-Infantes, EstefaníaDíaz, IreneHitos, Ana BelénCahuana, Gladys MargotMartínez-Ruiz, AntonioSoria-Juan, BárbaraRodríguez-Griñolo, RosarioHmadcha, AbdelkrimMartín, FranzSoria, BernatTejedo, Juan R.Bedoya, Francisco Javier2022-12-092022-12-092021-09-02Caballano-Infantes E, Díaz I, Hitos AB, Cahuana GM, Martínez-Ruiz A, Soria-Juan B, et al. Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide. Antioxidants. 2021 Sep 2;10(9):1408http://hdl.handle.net/10668/4473The optimization of conditions to promote the stemness of pluripotent cells in vitro is instrumental for their use in advanced therapies. We show here that exposure of human iPSCs and human ESCs to low concentrations of the chemical NO donor DETA/NO leads to stabilization of hypoxia-inducible factors (HIF-1α and HIF-2α) under normoxia, with this effect being dependent on diminished Pro 402 hydroxylation and decreased degradation by the proteasome. Moreover, the master genes of pluripotency, NANOG and OCT-4, were upregulated. NO also induces a shift in the metabolic profile of PSCs, with an increased expression of hypoxia response genes in glycolysis. Furthermore, a reduction in the mitochondrial membrane potential with lower oxygen consumption and increased expression of mitochondrial fusion regulators, such as DRP1, was observed. The results reported here indicate that NO mimics hypoxia response in human PSCs and enhances their stemness properties when cultured under normoxic conditions.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/PluripotencyNormoxiaNitric oxideHypoxiaMetabolismHydroxylationMitochondriaMitochondrial membranesProteasome inhibitorOxygen consumptionGlycolysisPluripotent stem cellsÓxido nítricoHipoxiaMetabolismoHidroxilaciónMitocondriasMembranas mitocondrialesInhibidores de proteasomaConsumo de oxígenoGlucólisisCélulas madre pluripotentesMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides::DEETMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::HydroxylationMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Energy Metabolism::Proton-Motive Force::Membrane Potential, MitochondrialMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Mitochondrial Turnover::Mitochondrial DynamicsMedical Subject Headings::Chemicals and Drugs::Macromolecular Substances::Multiprotein Complexes::Multienzyme Complexes::Proteasome Endopeptidase ComplexMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Oxygen ConsumptionMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::MetabolomeMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Carbohydrate Metabolism::GlycolysisMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Basic Helix-Loop-Helix Transcription FactorsMedical Subject Headings::Anatomy::Cells::Stem Cells::Pluripotent Stem CellsMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Free Radicals::Nitric OxideMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Signs and Symptoms, Respiratory::AnoxiaMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::MetabolismMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::HydroxylationMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors::Proteasome Inhibitorsresearch article34573040Acceso abierto10.3390/antiox100914082076-3921PMC8472328