Autor según el artículo: Fernández-Arroyo S, Cuyàs E, Bosch-Barrera J, Alarcón T, Joven J, Menendez JA.
Departamento: Medicina i Cirurgia
Autor/es de la URV: FERNANDEZ ARROYO, SALVADOR / Joven Maried, Jorge
Palabras clave: Stem cells S-adenosylhomocysteine One-carbon metabolism Ips cells Homocysteine s-adenosylhomocysteine one-carbon metabolism ips cells homocysteine
Resumen: Generation of induced pluripotent stem (iPS) cells and cancer biogenesis share similar metabolic switches. Most studies have focused on how the establishment of a cancer-like glycolytic phenotype is necessary for the optimal routing of somatic cells for achieving stemness. However, relatively little effort has been dedicated towards elucidating how one-carbon (1C) metabolism is retuned during acquisition of stem cell identity. Here we used ultra-high pressure liquid chromatography coupled to an electrospray ionization source and a triple-quadrupole mass spectrometer [UHPLC-ESI-QqQ-MS/MS] to quantitatively examine the methionine/folate bi-cyclic 1C metabolome during nuclear reprogramming of somatic cells into iPS cells. iPS cells optimize the synthesis of the universal methyl donor S-adenosylmethionine (SAM), apparently augment the ability of the redox balance regulator NADPH in SAM biosynthesis, and greatly increase their methylation potential by triggering a high SAM:S-adenosylhomocysteine (SAH) ratio. Activation of the methylation cycle in iPS cells efficiently prevents the elevation of homocysteine (Hcy), which could alter global DNA methylation and induce mitochondrial toxicity, oxidative stress and inflammation. In this regard, the methyl donor choline is also strikingly accumulated in iPS cells, suggesting perhaps an overactive intersection of the de novo synthesis of choline with the methionine-Hcy cycle. Activation of methylogenesis and maintenance of an optimal SAM:Hcy ratio might represent an essential function of 1C metabolism to provide a labile pool of methyl groups and NADPH-dependent redox products required for successfully establishing and maintaining an embryonic-like DNA methylation imprint in stem cell states.
Áreas temáticas: Oncology Medicina i Cancer research
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: jorge.joven@urv.cat
Identificador del autor: 0000-0003-2749-4541
Fecha de alta del registro: 2023-02-18
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
Enlace a la fuente original: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735514/
Referencia al articulo segun fuente origial: Oncoscience. 2 (12): 958-967
Referencia de l'ítem segons les normes APA: Fernández-Arroyo S, Cuyàs E, Bosch-Barrera J, Alarcón T, Joven J, Menendez JA. (2015). Activation of the methylation cycle in cells reprogrammed into a stem cell-like state. Oncoscience, 2(12), 958-967. DOI: 10.18632/oncoscience.280
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI del artículo: 10.18632/oncoscience.280
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2015
Tipo de publicación: Journal Publications