Vitamin C and Somatic Cell Reprogramming

Vitamin C plays a pivotal role in somatic cell reprogramming by enhancing the activity of numerous epigenetic regulators belonging to a broad family of Fe2+ and α-ketoglutarate-dependent dioxygenases (α-KGDDs). Vitamin C potentiates the activity of histone and DNA demethylating α-KGDDs, leading to the erasure of epigenetic modifications across the genome of somatic cells that increases the efficiency of reprogramming, and quality of induced pluripotent stem cells (iPSCs). Stem cell therapies developed from iPSCs are currently being sought after for numerous applications in regenerative medicine that could be greatly improved by vitamin C supplementation. Recent studies have also drawn attention to vitamin C's role in the hematopoietic system. Vitamin C deficiency leads to defects in hematopoiesis that can accelerate leukemia progression. Treatment with vitamin C specifically enhances the activity of α-KGDDs, such as the ten-eleven translocation (TET) proteins, that are important tumor suppressors of the hematopoietic lineages, leading to a block in aberrant hematopoietic stem cell self-renewal and leukemia progression. The discovery that vitamin C can modulate the activity of α-KGDDs to target the epigenome of reprogrammed cells, stem cells, and cancer cells has important application in the treatment of human diseases.