dc.contributor.author
Fernández-Arroyo, S.
dc.contributor.author
Cuyas, E.
dc.contributor.author
Bosch-Barrera, J.
dc.contributor.author
Alarcon, T.
dc.contributor.author
Joven, J.
dc.contributor.author
Menendez, J.A.
dc.date.accessioned
2020-11-16T09:38:45Z
dc.date.accessioned
2024-09-19T14:33:08Z
dc.date.available
2020-11-16T09:38:45Z
dc.date.available
2024-09-19T14:33:08Z
dc.date.issued
2015-01-01
dc.identifier.uri
http://hdl.handle.net/2072/377777
dc.format.extent
10 p.
cat
dc.relation.ispartof
Oncoscience
cat
dc.rights
L'accés als continguts d'aquest document queda condicionat a l'acceptació de les condicions d'ús establertes per la següent llicència Creative Commons:http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.source
RECERCAT (Dipòsit de la Recerca de Catalunya)
dc.subject.other
Matemàtiques
cat
dc.title
Activation of the methylation cycle in cells reprogrammed into a stem cell-like state
cat
dc.type
info:eu-repo/semantics/article
cat
dc.type
info:eu-repo/semantics/publishedVersion
cat
dc.local.notes
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.
cat
dc.rights.accessLevel
info:eu-repo/semantics/openAccess
