Remembrance of things past – how some stem cells remember what they used to be

Can you tell the difference? Embryonic (left) and iPS cells side by side

First there were embryonic stem cells. Then came induced pluripotent stem (iPS) cells, which start out as adult cells, such as skin cells. Using a variety of methods, scientists can turn these adult cells into iPS cells, which can then be changed or turned into any kind of tissue, just as embryonic stem cells can.

These iPS cells offer advantages over their embryonic cousins. In theory, transplant tissue could be created from a patient’s own cells, reducing the risk of an immune response such as often happens after a kidney or liver transplant. It’s a neat idea, but we have to learn more about iPS cells to make it work. In particular, we need to figure out the differences between induced pluripotent and embryonic stem cells.

Ideally, iPS cells would be a clean slate, retaining no evidence they’d ever even been an adult cell. But scientists have long known that iPS cells retain a certain amount of “memory” from their former lives as adult cells.

Now, CIRM-funded researchers at UCLA, and elsewhere, have published a study in Stem Cell Reports that identifies some important differences between embryonic stem and iPS cells. They focused on a process called methylation, in which molecules called methyl groups attach to DNA to silence a gene. Methylation is a sub-discipline of epigenetics, which studies how genes get turned on and off.

Methylation is a big deal because, as our bodies develop, some genes become unnecessary and need to be silenced, while other genes have to step up and orchestrate the next job. The researchers wanted to know whether methylation patterns were different between iPS and embryonic stem cells. Turns out they are.

The study found that, quite often, iPS cells retain old methylation patterns from when they were adults, remembrance of things past. Some genes were even more methylated than usual—hypermethylated—when compared to either embryonic stem cells or fully formed adult cells. Apparently, the process of reprogramming adult cells to stem cells changes their methylation profiles, turning off genes associated with immunity and cellular housekeeping.

This new information provides researchers a series of biomarkers to distinguish between embryonic and induced pluripotent stem cells. In addition, illuminating how this important mechanism differs in iPS cells could make them more useful in the long run.

Josh Baxt