Babies can be anything when they grow up, but it's a lot harder for a 45-year-old accountant to start a new life as a firefighter. Likewise, embryonic stem cells can become any kind of cell in the human body, but it's another thing entirely to force a specialized adult cell out of its comfort zone. For instance, scientists can strip an adult blood cell of its programming, and make it act like a stem cell again. But the results aren't perfect. And, now, it looks like these "induced pluripotent stem cells" (or iPSCs) are even more flawed than researchers previously realized. Science blogger extraordinaire Ed Yong explains:
The history of iPSCs is written in molecular marks that annotate its DNA. These 'epigenetic' changes can alter the way a gene behaves even though its underlying DNA sequence is still the same. They are like Post-It notes – you can stick them to a book to point out parts to read or ignore, without editing the underlying text. Epigenetic marks separate different types of cells from one another, influencing which genes are switched on and which are switched off. And according to Kim, they're not easy to remove, even when the cell has apparently been reprogrammed into a stem-like state.
He focused on one such marker – the presence of methyl groups on DNA, which typically serve to switch off genes. They're like Post-it notes that say "Ignore this". Kim found that iPSCs have very different methylation patterns depending on the cells they came from. Those that come from brain or connective cells have methyl groups at genes that are necessary for making blood cells, and vice versa. The iPSCs even have distinctive methyl marks if they come from slightly different lineages of blood cells.
Now, Ryan Lister and Mattia Pelizzola from The Salk Institute have found the same reprogramming errors in human iPSCs, and to a much greater extent than even Kim had suspected.
At first, the iPSCs seemed to have a spread of methyl marks that looked superficially similar to those of embryonic cells. But when Lister and Pelizzola looked more closely, the cracks started to appear in this tidy picture. The duo found plenty of hotspots around the iPSC genomes that were unusually ridden with methyl marks. None of these marks existed in true embryonic stem cells, and some sat in places that could switch off important genes.
That's a problem. There might be ways around it, Ed says. And there are other ways to turn adult cells into stem cells. Trouble is, none of those technologies are as well-developed, and they're more likely to spark ethical debates. If we're going to be able to use stem cells in a really productive, wide-spread way, this is a big hurdle that will have to be cleared.
Why didn't we know this earlier? Because the path of research is long, winding, and bumpy. To get an idea of what it took to get to this point, check out the awesome interactive timeline Ed made to accompany this story.
Not Exactly Rocket Science: Reprogrammed stem cells are loaded with errors
