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Journal Articles (Data Paper) Nature Metabolism Year : 2023

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

Abstract

Abstract 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 B 12 and molecular hallmarks of methionine starvation. Supplementation with vitamin B 12 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 B 12 levels, providing evidence for a link between B 12 levels, H3K36 methylation, transcriptional fidelity and efficient reprogramming. Vitamin B 12 supplementation also accelerates tissue repair in a model of ulcerative colitis. We conclude that vitamin B 12 , 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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hal-04596678 , version 1 (06-06-2024)

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Marta Kovatcheva, Elena Melendez, Dafni Chondronasiou, Federico Pietrocola, Raquel Bernad, et al.. Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair. Nature Metabolism, 2023, 5 (11), pp.1911-1930. ⟨10.1038/s42255-023-00916-6⟩. ⟨hal-04596678⟩
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