Induced pluripotent stem cells (iPSCs) are similar to embryonic stem cells (ESCs), which are made from embryos, but these two types of stem cells have some distinct differences. iPSCs for instance, are somewhat slow to grow than their ESC counterparts. They also have a capacity to form nerve cells (neurons), but they also do so somewhat inefficiently.
Now a group has identified particular genetic differences between iPSCs and ESCs and this might determine why these two types of stem cells show different growth characteristics. This study examined mouse iPSCs and ESCs, and if confirmed in humans, such a finding might help clinicians to select only the best stem cells for therapeutic applications and disease modeling.
iPSCs are created by reprogramming adult cells. They resemble ESCs in that both cell types are pluripotent, which is to say that they can form any tissue in the body.
A team at Massachusetts General Hospital, led by Konrad Hochedlinger, has now made iPSCs and ESCs with identical DNA, and the iPSCs incorporated into chimeric mice with a much poorer efficiency than ESCs. Because such incorporation experiments are a standard test of pluripotency. They added the iPSCs and ESCs into embryos from mice of that have different colored fur. Once each mouse matures, the color of its fur coat reveals how well the stem cells contributed to forming its skin. ESCs contributed much more robustly to the fur of the mice than did iPSCs.
Secondly, when these scientists compared genome-wide gene expression patterns in ESCs and iPSCs, they discovered that a small stretch of DNA on the long arm of chromosome 12 had very different levels of gene activity. In this region, two genes and a slew of tiny regulatory sequences called microRNAs were consistently activated in the ESCs, but silenced in iPSCs regardless of whether the reprogrammed cells came originally from skin, brain, blood or other tissue. The function of the key genes in this region are unknown, but this region is usually silenced in mouse sperm cells and activated in other types of cell, so reprogramming might somehow mimic the silencing process.
This discovery implies that human iPSCs carry similarly silenced sequences that make them less effective than ES cells.
Although iPSCs in these experiments did not meet the strictest criteria of stemness, since they did not introduce significant coloring into the fur of chimeric mice, but they may still have been able to form many types of tissue, something the researchers did not explicitly test.
Although findings in mice don’t always apply to humans, if a similar gene signatures are found in human iPSCs, it could help researchers to identify which iPSCs to avoid using, and which stand the best chance of producing a desired tissue. Hochedlinger’s team has therefore begun to look at human ES and iPSCs in search of similar gene-activity patterns to those they found in mice.