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

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Kovatcheva, Marta | Melendez, Elena | Chondronasiou, Dafni | Pietrocola, Federico | Bernad, Raquel | Caballe, Adrià | Junza, Alexandra | Capellades, Jordi | Holguín-Horcajo, Adrián | Prats, Neus | Durand, Sylvere | Rovira, Meritxell | Yanes, Oscar | Stephan-Otto Attolini, Camille | Kroemer, Guido | Serrano, Manuel

Edité par CCSD ; Nature Publishing Group -

International audience. 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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