"This type of research gets to the fabric of the fundamental differences between stem cells and their parental cells," says Akiko Doi, a doctoral candidate in the graduate program in Cellular and Molecular Medicine at Johns Hopkins. "Clearly, that fabric involves these DMRs, which are essential to our understanding the nature of these potentially therapeutic iPS cells."

As scientists learn more about the epigenetics of reprogrammed cells, they may find new ways of creating them or using them. "If we discover that certain genes or regions are altered in iPS cells," says Feinberg, "then we might be able to target these and come up with new ways of approaching stem cell therapy.

"We can try to correlate these differences with the ways these iPS cells behave, and answer questions such as which ones are more stable and which ones form tumors. If we can use the epigenetic information to characterize these cells, this could inform how we might use them therapeutically."

Adds Daley, director of the Stem Cell Transplantation Program at HHMI/Children's Hospital in Boston, "Our data also point to differences between iPS cells and embryonic stem (ES) cells, which everyone has felt were similar if not identical. Such differences may prove important in the behavior of iPS cells in studies on tissue formation and may complicate therapies based on iPS cells. We need to develop ways of generating iPS cells that are a closer match to ES cells in their methylation patterns. Only then will we be confident that iPS cells are a safe replacement for ES cells in research and therapy."

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