In the second study in Nature, researchers from Canada and Finland used microarrays—chips dotted with pieces of target DNA—to analyze another type of genetic mutation in iPS cells: small deletions or duplications of DNA known as structural variations. They found that iPS cells had more of these variations than either skin cells or embryonic stem cells did early in the reprogramming process but that cells bearing abnormalities quickly died off as the population continued to grow.
Researchers say that more research is needed to understand what the findings mean for future use of these cells in therapies. “The big question is which of these changes really matter,” says Jeanne Loring, director of the Center for Regenerative Medicine at Scripps Research Institute. “We need to figure out which are relevant and which are just noise.” Loring has published results similar to the second study this year.
“For some type of genetic changes—mutations in cancer-linked genes, for example—we clearly would not want to use cells in patients,” says Martin Pera, director of the Broad Center for Regenerative Medicine at the University of Southern California, who wrote a commentary accompanying the publication in Nature. “But for the vast range of changes, we don’t really understand functional significance.” As is the case in many genomics studies, “the ability to collect in-depth genetic information has outstripped our ability to interpret it,” he says. “That’s the real challenge going forward.”
Part of the problem is that scientists know little about the mechanisms underlying reprogramming. “We can’t yet identify what particular aspect of the reprogramming process or cell culture is responsible for engendering these changes,” says Pera. “If we want to fix this, we need to understand what aspect of the process is critical.”