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

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

  • Nat Metab. 2023 Nov 16. doi: 10.1038/s42255-023-00916-6.
Marta Kovatcheva 1,  Elena Melendez 2,  Dafni Chondronasiou 2,  Federico Pietrocola 2 3,  Raquel Bernad 2,  Adrià Caballe 2,  Alexandra Junza 4 5,  Jordi Capellades 4 6,  Adrián Holguín-Horcajo 7 8,  Neus Prats 2,  Sylvere Durand 9 10,  Meritxell Rovira 7 8,  Oscar Yanes 4 5,  Camille Stephan-Otto Attolini 2,  Guido Kroemer 9 10 11,  Manuel Serrano 12 13 14
Affiliations

Affiliations

  • 1 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. marta.kovatcheva@irbbarcelona.org.
  • 2 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
  • 3 Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
  • 4 Universitat Rovira i Virgili, Department of Electronic Engineering, IISPV, Tarragona, Spain.
  • 5 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
  • 6 Institut d'Investigació Sanitària Pere Virgili (IISPV), Metabolomics Platform, Reus, Spain.
  • 7 Department of Physiological Science, School of Medicine, Universitat de Barcelona (UB), L'Hospitalet de Llobregat, Spain.
  • 8 Pancreas Regeneration: Pancreatic Progenitors and Their Niche Group, Regenerative Medicine Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
  • 9 Metabolomics and Cell Biology Platforms UMS AMMICa/UMR 1138, Institut Gustave Roussy, Villejuif, France.
  • 10 Equipe labellisée par la Ligue contre le cancer, Centre de Recherche des Cordeliers, Inserm U1138, Université de Paris, Sorbonne Université, Institut Universitaire de France, Paris, France.
  • 11 Institut du Cancer Paris CARPEM, Department of Biology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
  • 12 Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. mserrano@altoslabs.com.
  • 13 Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain. mserrano@altoslabs.com.
  • 14 Altos Labs, Cambridge Institute of Science, Cambridge, UK. mserrano@altoslabs.com.
PMID: 37973897 DOI: 10.1038/s42255-023-00916-6
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.

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