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

Identificador:  imarina:9332029

Handle: https://hdl.handle.net/20.500.11797/imarina9332029

Autores:  Kovatcheva, M; Melendez, E; Chondronasiou, D; Pietrocola, F; Bernad, R; Caballe, A; Junza, A; Capellades, J; Holguín-Horcajo, A; Prats, N; Durand, S; Rovira, M; Yanes, O; Attolini, CSO; Kroemer, G; Serrano, M

Resumen:
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. The Author(s).