Vitamins A and C help erase 'memory' in stem cells
Vitamins A and C can enhance success in the challenging process
of converting adult cells into stem cells, an international study co-led
by a University of Otago researcher has found.
The research team discovered that the two vitamins complement each other in erasing "memory" associated with DNA, an important effect for improving technologies geared towards regenerative medicine and stem cell therapy.
The findings are published this week in Proceedings of the National Academy of Science (PNAS).
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.
Study co-lead author Dr Tim Hore of Otago’s Department of Anatomy says that 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.
"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," Dr Hore says.
He says that 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.
Dr Hore was previously a Human Frontier Long Term Fellow at the UK’s Babraham Institute. Along with collaborators at Babraham and in Stuttgart, Germany, he 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 "naïve" embryonic characteristics were created in much greater numbers, he says.
The mechanism by which this occurs was also detailed in the study.
"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 says.
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.
"Along with other Otago research groups, my lab is 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 says.
This work was funded by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the European Union EpiGeneSys Network of Excellence, the European Union BLUEPRINT Consortium (awarded to senior author, Professor Wolf Reik), the Human Frontier Science Program (Dr Tim Hore), the Swiss National Science Foundation/Novartis (Dr Ferdinand von Meyenn) and the German Research Foundation (Associate Professor Tomasz Jurkowski).
The research team discovered that the two vitamins complement each other in erasing "memory" associated with DNA, an important effect for improving technologies geared towards regenerative medicine and stem cell therapy.
The findings are published this week in Proceedings of the National Academy of Science (PNAS).
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.
Study co-lead author Dr Tim Hore of Otago’s Department of Anatomy says that 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.
"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," Dr Hore says.
He says that 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.
Dr Hore was previously a Human Frontier Long Term Fellow at the UK’s Babraham Institute. Along with collaborators at Babraham and in Stuttgart, Germany, he 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 "naïve" embryonic characteristics were created in much greater numbers, he says.
The mechanism by which this occurs was also detailed in the study.
"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 says.
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.
"Along with other Otago research groups, my lab is 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 says.
This work was funded by the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, the Medical Research Council, the European Union EpiGeneSys Network of Excellence, the European Union BLUEPRINT Consortium (awarded to senior author, Professor Wolf Reik), the Human Frontier Science Program (Dr Tim Hore), the Swiss National Science Foundation/Novartis (Dr Ferdinand von Meyenn) and the German Research Foundation (Associate Professor Tomasz Jurkowski).
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Labels: DNA methylation, erase, memory, regenerative therapy, Stem cells, Vitamins A and C
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