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

Marta Kovatcheva1, Elena Melendez2, Dafni Chondronasiou2

  • 1Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. marta.kovatcheva@irbbarcelona.org.

Nature Metabolism
|November 17, 2023
PubMed

Insights

Vitamin B12 (cobalamin) is crucial for transient reprogramming, a method for tissue regeneration. Supplementing vitamin B12 enhances reprogramming efficiency and accelerates tissue repair by influencing epigenetic dynamics and one-carbon metabolism.

Area of Science:

  • Cellular reprogramming
  • Epigenetics
  • Metabolic pathways

Background:

  • Transient reprogramming using OCT4, SOX2, KLF4, and MYC (OSKM) shows therapeutic potential for tissue regeneration.
  • The metabolic demands of OSKM reprogramming are not well understood.

Purpose of the Study:

  • To investigate the metabolic requirements of OSKM reprogramming.
  • To determine the role of vitamin B12 in reprogramming efficiency and tissue repair.

Main Methods:

  • OSKM reprogramming was induced in mice and cultured cells.
  • Vitamin B12 levels and methionine metabolism were assessed.
  • Epigenetic marks, specifically H3K36me3, were analyzed.
  • Tissue repair was evaluated in a model of ulcerative colitis.

Main Results:

  • OSKM reprogramming led to global vitamin B12 depletion and methionine starvation.
  • Vitamin B12 supplementation enhanced reprogramming efficiency in both mice and cell cultures.
  • Vitamin B12 levels were directly linked to H3K36me3 methylation, transcriptional fidelity, and reprogramming efficiency.
  • Vitamin B12 supplementation accelerated tissue repair in an ulcerative colitis model.

Conclusions:

  • Vitamin B12 is essential for efficient in vivo reprogramming and tissue repair.
  • Vitamin B12 influences reprogramming through its role in one-carbon metabolism and epigenetic regulation.
  • Targeting vitamin B12 metabolism could be a therapeutic strategy to improve reprogramming-based regenerative medicine.

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