Author, as appears in the article.: Fernández-Arroyo S, Cuyàs E, Bosch-Barrera J, Alarcón T, Joven J, Menendez JA.
Department: Medicina i Cirurgia
URV's Author/s: FERNANDEZ ARROYO, SALVADOR / Joven Maried, Jorge
Keywords: Stem cells S-adenosylhomocysteine One-carbon metabolism Ips cells Homocysteine s-adenosylhomocysteine one-carbon metabolism ips cells homocysteine
Abstract: 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.
Thematic Areas: Oncology Medicina i Cancer research
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: jorge.joven@urv.cat
Author identifier: 0000-0003-2749-4541
Record's date: 2023-02-18
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735514/
Papper original source: Oncoscience. 2 (12): 958-967
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
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Article's DOI: 10.18632/oncoscience.280
Entity: Universitat Rovira i Virgili
Journal publication year: 2015
Publication Type: Journal Publications