Vitamin B12 is a limiting factor for induced cellular plasticity and tissue repair.
Nat Metab
; 5(11): 1911-1930, 2023 Nov.
Article
em En
| MEDLINE
| ID: mdl-37973897
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 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Reprogramação Celular
/
Plasticidade Celular
Idioma:
En
Revista:
Nat Metab
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Espanha