Epigenetics researchers at the Babraham Institute in Cambridge UK have identified the biological process that leads to global loss of the genomes methylation memory when cells are reprogrammed at fertilisation to the so-called ground-state development.

Epigenetics is revolutionising our understanding of genetic inheritance and also helping to explain how our genes can be influenced by the environment. Genomic methylation, which does not alter DNA sequence but essentially marks it in a stable lifelong manner, is accumulated during development and plays a vital role in committing cells to specialised roles in the body.

These methylation marks must be erased at the start of each new generation, to restore the ability of a newly fertilised egg to develop into a new organism.

Understanding this mechanism of wiping the slate clean is important to appreciate how the developmental capacity of cells is reset and also provides insights that will guide the use of stem cells for therapeutic purposes, which also requires remodelling of genomic methylation.

It is known that when adult cells are reprogrammed to stem cell-like cells, they do not completely erase their memory. This unfortunately limits their use in stem cell therapy since these cells will have the tendency to develop into the types of specialised cells from which they were originally derived.

Stem cells receive signals from the environment that force them to become more specialised cells. The Babraham researchers blocked these environmental signals with drugs and found that they could induce this superior stem cell state with the treatment.

In a parallel study published recently in Nature, researchers from The University of California San Francisco and The University of British Columbia in Canada found that treating stem cells with Vitamin C had similar effects, suggesting that nutritional factors may lead to better stem cells.

Dr Gabriella Ficz, lead author from the Babraham Institute said: We were quite surprised by the strong mechanistic link between the external signals and the DNA methylation machinery.

This work consequently opens up a whole range of questions related to what happens in the adult body where we know that aberrant methylation is associated with cancer.

In addition, how these changes are mediated through the new DNA modification 5-hydroxymethylcytosine (5-hmC), similar to what we have observed in ES cells, remains a key focus in epigenetics research.

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Babraham scientists make stem cell discovery