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oai:recercat.cat:2445/2041192025-12-05T09:24:29Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478908col_2072_478917

Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair 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 Vitamines hidrosolubles Epigenètica Water-soluble vitamins Epigenetics 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 2023-12-05T12:17:24Z 2023-12-05T12:17:24Z 2023-11-16 2023-12-05T12:17:25Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1038/s42255-023-00916-6 Nature Metabolism, 2023, vol. 5, p. 1911-1930 https://doi.org/10.1038/s42255-023-00916-6 cc-by (c) Marta Kovatcheva et al., 2023 http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Nature Publishing Group Articles publicats en revistes (Ciències Fisiològiques)