Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair

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 h...

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Detalles Bibliográficos
Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/204119
Acceso en línea:https://hdl.handle.net/2445/204119
Access Level:acceso abierto
Palabra clave:Vitamines hidrosolubles
Epigenètica
Water-soluble vitamins
Epigenetics
Descripción
Sumario: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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