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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/204119
Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair
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Transient reprogramming by the expression of OCT4, SOX2, KLF4 and MYC (OSKM) is a therapeutic strategy for tissue regeneration and rejuvenation, but little is known about its metabolic requirements. Here we show that OSKM reprogramming in mice causes a global depletion of vitamin B12 and molecular hallmarks of methionine starvation. Supplementation with vitamin B12 increases the efficiency of reprogramming both in mice and in cultured cells, the latter indicating a cell-intrinsic effect. We show that the epigenetic mark H3K36me3, which prevents illegitimate initiation of transcription outside promoters (cryptic transcription), is sensitive to vitamin B12 levels, providing evidence for a link between B12 levels, H3K36 methylation, transcriptional fidelity and efficient reprogramming. Vitamin B12 supplementation also accelerates tissue repair in a model of ulcerative colitis. We conclude that vitamin B12, through its key role in one-carbon metabolism and epigenetic dynamics, improves the efficiency of in vivo reprogramming and tissue repair
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KOVATCHEVA, Marta, MELÉNDEZ ESTEBAN, Elena, CHONDRONASIOU, Dafni, PIETROCOLA, Federico, BERNAD, Raquel, CABALLÉ MESTRES, Adrià, JUNZA MARTÍNEZ, Alexandra, CAPELLADES, Jordi, HOLGUÍN HORCAJO, Adrián, PRATS, Neus, DURAND, Sylvere, ROVIRA, Meritxell, YANES, Oscar, STEPHAN-OTTO ATTOLINI, Camille, KROEMER, Guido, SERRANO MARUGÁN, Manuel. Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair. _Nature Metabolism_. 2023. Vol. 5, núm. 1911-1930. [consulta: 20 de gener de 2026]. ISSN: 2522-5812. [Disponible a: https://hdl.handle.net/2445/204119]