The Hidden Code of Stem Cells

The DNA of embryonic stem cells has a unique label, which could help scientists figure out how to manipulate such cells for therapeutic uses.

The DNA of embryonic stem cells is labeled in a unique and characteristic way, according to new research from scientists in California. The pattern could shed light on how embryonic stem cells maintain their ability to become any type of cell and might also help efforts to clone these cells, allowing scientists to develop better stem cell therapies.

Embryonic stem cells have the ability to become virtually any cell in the body, making them the basis for potential therapies to treat everything from Parkinson's disease to diabetes. But before these cells can be developed into useful therapies, scientists must better understand the genetic root of the cells' unique properties -- and learn to control them.

"It's very likely that these [labels] point to regions of the genome that are crucial for maintaining the self-renewing capacity of embryonic stem cells," says James Battey, chair of the Stem Cell Task Force at the National Institutes of Health in Bethesda, MD.

Epigenetic changes to DNA are those that alter expression of certain genes, for instance by reversibly tagging those genes, without changing the sequence of the DNA itself. In a paper published last week in Genome Research, researchers studied one such process, called DNA methylation, in which certain molecules within the gene are chemically modified, altering the activity of that particular gene.

Scientists have previously been able to study DNA methylation in a single or a few genes. But in the new study, researchers developed a technology to look at methylation patterns in hundreds of genes at a time.

Jian-Bing Fan, research director at Illumina, a gene analysis company based in San Diego, CA, modified the company's gene microarrays -- tiny chips labeled with specific sequences of DNA -- so that they could simultaneously detect DNA methylation at 1,500 sites in the genome.

Researchers then analyzed 14 lines of embryonic stem cells, as well as adult cells and cancer cells. They found that the embryonic stem cells had a unique methylation pattern, regardless of where the cells came from or how they were generated. That pattern was significantly different from patterns found in adult stem cells, adult differentiated cells, and cancer cell lines.

"All our collaborators at 11 institutions across the world were surprised to see such a unique signature, given that all lines come from people of different ethnic origins and were isolated and grown under different conditions," says Fan.

The findings could help stem cell scientists in numerous ways. For example, one concern associated with stem cell-based therapies is that they could form tumors when injected into the body -- embryonic stem cells share some qualities of cancer cells, notably, their ability to divide indefinitely. But the findings show that the two cells types are actually very different.