Vitamins A and C complement each other in erasing "memory" associated with DNA, an important effect for improving technologies geared towards regenerative medicine and stem cell therapy, scientists have found. The two vitamins can enhance success in the challenging process of converting adult cells into stem cells, an international team including researchers from University of Otago in New Zealand have found. Ordinary adult cells, such as those in the skin or blood, can be artificially coerced in a culture dish to resemble embryos only a few days old. Since the 2006 discovery that this remarkable reprogramming process is possible, there has been much interest in using induced embryonic stem cells to cure human disease, said Tim Hore from Otago. "However, hampering these efforts is the reality that adult cells are resistant to changes in their identity, partly because of chemical alterations to their DNA," said Hore, who was previously with the Babraham Institute in the UK. He said these alterations, known as "DNA methylation" are acquired during development and provide a form of cellular memory that helps cells faithfully maintain a specialised function. Removal of this memory is critical in order to create a developmentally potent stem cell, or to change one kind of adult cell to another. Hore determined that adding vitamins A and C to culture dishes synergistically removes DNA methylation from embryonic stem cells. When applied to cells during the reprogramming process, those with the desired "naive" embryonic characteristics were created in much greater numbers, he said. "We found that both vitamins affect the same family of enzymes which actively remove DNA methylation; it turns out that vitamin A increases the number of these enzymes within the cell, and vitamin C enhances their activity," he said. In addition to regenerative medicine, this work may have implications for other areas of biomedical importance.
Loss of DNA methylation and cellular memory are a hallmark of certain cancers, so a better understanding of how this process occurs could prove significant. "We are beginning to explore how the vitamin-induced effects we have uncovered in this study might impact on the loss of DNA methylation in certain cancers," he said. The study appears in the journal Proceedings of the National Academy of Science (PNAS).
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