Autor segons l'article: Fernández-Arroyo S, Cuyàs E, Bosch-Barrera J, Alarcón T, Joven J, Menendez JA.
Departament: Medicina i Cirurgia
Autor/s de la URV: FERNANDEZ ARROYO, SALVADOR / Joven Maried, Jorge
Paraules clau: Stem cells S-adenosylhomocysteine One-carbon metabolism Ips cells Homocysteine s-adenosylhomocysteine one-carbon metabolism ips cells homocysteine
Resum: 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.
Àrees temàtiques: Oncology Medicina i Cancer research
Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
Adreça de correu electrònic de l'autor: jorge.joven@urv.cat
Identificador de l'autor: 0000-0003-2749-4541
Data d'alta del registre: 2023-02-18
Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
Enllaç font original: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735514/
Referència a l'article segons font original: Oncoscience. 2 (12): 958-967
Referència 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 Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
DOI de l'article: 10.18632/oncoscience.280
Entitat: Universitat Rovira i Virgili
Any de publicació de la revista: 2015
Tipus de publicació: Journal Publications