RT Journal Article
T1 Stemness of Human Pluripotent Cells: Hypoxia-Like Response Induced by Low Nitric Oxide
A1 Caballano-Infantes, Estefanía
A1 Díaz, Irene
A1 Hitos, Ana Belén
A1 Cahuana, Gladys Margot
A1 Martínez-Ruiz, Antonio
A1 Soria-Juan, Bárbara
A1 Rodríguez-Griñolo, Rosario
A1 Hmadcha, Abdelkrim
A1 Martín, Franz
A1 Soria, Bernat
A1 Tejedo, Juan R.
A1 Bedoya, Francisco Javier
K1 Pluripotency
K1 Normoxia
K1 Nitric oxide
K1 Hypoxia
K1 Metabolism
K1 Hydroxylation
K1 Mitochondria
K1 Mitochondrial membranes
K1 Proteasome inhibitor
K1 Oxygen consumption
K1 Glycolysis
K1 Pluripotent stem cells
K1 Óxido nítrico
K1 Hipoxia
K1 Metabolismo
K1 Hidroxilación
K1 Mitocondrias
K1 Membranas mitocondriales
K1 Inhibidores de proteasoma
K1 Consumo de oxígeno
K1 Glucólisis
K1 Células madre pluripotentes
AB The 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.
PB MDPI
YR 2021
FD 2021-09-02
LK http://hdl.handle.net/10668/4473
UL http://hdl.handle.net/10668/4473
LA en
NO Caballano-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):1408
DS RISalud
RD Apr 7, 2025