Vitamin C deprivation puts stem cells to sleep

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https://ashpublications.org/blood/artic ... s-to-sleep

In this issue of Blood, Comazzetto et al1 demonstrate that vitamin C deprivation promotes stem cell quiescence and functionally reprograms multipotent hematopoietic progenitors (MPPs) to acquire hematopoietic stem cell (HSC)-like properties, such as enhanced self-renewal and reconstitution potential (see figure).


Ascorbate (vitamin C) is a potent regulator of stem cell function and acts as a suppressor of leukemia.2,3 Two studies published in 2017 in the journals Cell2 and Nature3 demonstrated that vitamin C suppresses leukemogenesis through its ability to modulate Tet2 function. Ascorbate acts as a cofactor for Tet2, enhancing its enzymatic activity. Tet2 is involved in the conversion of 5-methylcytosine to 5-hydroxymethylcytosine, a key step in the DNA demethylation process. In HSC, the loss of Tet2 promotes self-renewal4 and contributes to the development of myeloid neoplasia.4,5

Plasma levels of ascorbate can vary with age due to several factors including reduced dietary intake, impaired absorption, and altered ascorbate metabolism.10 Nonetheless, epidemiological studies revelated that individuals with low plasma ascorbate levels have higher risk of mortality from all causes including cancer, particularly among men.10 Furthermore, it is crucial to explore whether mutations in vitamin C transporters contribute to CH or if epigenetic silencing cooperates with clonal expansion and malignancy. Future studies should also investigate the double mutant (Slc23a2 and Tet2) in the context of aging and inflammation to determine whether these mice develop myeloid neoplasms more rapidly, which could provide valuable insights into the mechanisms driving age-related hematological disorders and the fine-tuning role vitamin C.