A study of mouse stem cells reveals that vitamin C may play a role in their health by influencing the switching on and off of genes. The researchers suggest this could have an important effect on the development of mice, humans and other animals, and finding out more about the underlying mechanisms could improve our understanding of in vitro fertilization, cancer and adult stem cells.
Senior author and stem-cell scientist Miguel Ramalho-Santos of the University of California San Francisco (UCSF) and colleagues write about their findings in a June 30th online issue of Nature. In cells, not all genes are active all the time. There is a regulated pattern of gene expression that switches genes on and off. This is held in the epigenome, the set of instructions that get passed on with DNA about how to control the DNA.
One of the mechanisms the epigenome uses to regulate gene expression is DNA methylation. In DNA methylation, the epigenome adds a methyl group to a selected point on the genome to stop certain genes from being expressed.
What Ramalho-Santos and colleagues discovered is that vitamin C plays a crucial role in helping to release the brakes that stop certain genes from being expressed in stem cells in embryos soon after fertilization when the sperm fuses with the egg.
The team came across the result while comparing different types of nutrient for growing mouse embryonic stem cells in the lab.
In a statement, Ramalho-Santos explains that they didn’t set out to find what they discovered, “We bumped into this result,” he adds.
He and his colleagues wanted to find out how different ingredients in the growth medium affected gene activity in the stem cells. They found adding vitamin C increased the enzyme activity that releases the brakes that normally hold back certain gene expressions.
Ramalho-Santos and colleagues discovered that vitamin C helps a group of enzymes called “Tet” that are active during early development, just after fertilization.
Tet acts on a wide array of methyl groups that are positioned along the DNA, these keep certain genes from being expressed. When Tet comes along, the genes are switched on as needed.
The team found that Tet enzymes require vitamin C for optimal activity. In the cultured cells, adding vitamin C to the nurturing medium caused gene activity to more faithfully follow the pattern that occurs in the early stages of mouse embryo development.
Ramalho-Santos says further studies should now explore how this discovery could have clinical uses. For example, they could look at whether adding vitamin C to the culture medium currently used in IVF improves results, and also, whether vitamin C can have an effect in certain cancers which are driven by faulty DNA methylation.
Stem-cell researchers may also start using vitamin C to help grow healthier stem cells, he adds.
A study published in Nature in 2011 suggests Tet plays an important role in stem cell reprogramming.
Another area to explore is whether vitamin C helps to maintain stem cell health in adult tissue. Recent studies have revealed that Tet enzymes are also active in adult tissue, not just in embryo development.
“… we anticipate that Vitamin C might also regulate Tet function in the adult,” says Ramalho-Santos.
The team now plans to further study the effect of vitamin C on Tet in live mice.
Funds from the National Institutes of Health, the California Institute of Regenerative Medicine and the Canadian Institutes of Health Research helped finance the study.
Written by Catharine Paddock PhD