Stem cells’ unassuming, bloblike appearance makes them hard to identify, but new research offers a way to blow their cover.
The technique can distinguish embryonic stem cells — which are pluripotent, meaning they can become any kind of cell in the body — from “adult” stem cells that reside in people’s organs and have a much more limited repertoire.
Using the new test, Jeanne Loring of the Scripps Research Institute in La Jolla, Calif., and her colleagues also provide fresh evidence that stem cells made by “reprogramming” a person’s skin cells without ever making or destroying an embryo are truly pluripotent, just like embryonic stem cells.
The findings, reported online August 24 in Nature, suggest that these reprogrammed, embryonic-like stem cells could be used for future stem cell therapies in place of embryonic cells, which are more controversial because they are extracted from embryos.
Scientists have debated whether reprogrammed cells truly have all the abilities of cells taken from embryos.
“You can do a pretty simple test now and discover if it’s pluripotent, and you couldn’t do that before,” Loring says.
To distinguish adult stem cells from pluripotent cells, Loring’s team compared the gene activity of about 150 stem cell samples of various types, including reprogrammed cells, embryonic stem cells and neural stem cells. Out of this comparison popped 299 interacting genes that form what the researchers call a pluripotency network, or PluriNet. Measuring the activity of these genes could reliably distinguish the different kinds of stem cells, the team reports.
“This is an exhaustive documentation of the essential gene expression features of pluripotency and will be a helpful roadmap for scientists working in this hot new area of biomedical research,” says George Daley of the Harvard Stem Cell Institute.
The way scientists have been testing the pluripotency of reprogrammed mouse cells is to add reprogrammed cells to mouse embryos and see whether the cells give rise to every type of body cell in the newborn pups. Such tests are difficult to perform with human cells for ethical reasons.
“People are always arguing about the differentiation potential and therapeutic potential of each of the various stem cells,” says Robb MacLellan, a cardiologist at the UCLA David Geffen School of Medicine. The new test is “going to help and speed up the development of this whole field.”
In 2006, Japanese researchers discovered a set of four genes that when injected into skin cells reprogram those cells into an embryonic-like state. Many of the 299 PluriNet genes encode proteins that are activated by this process, Loring says.
The test also found distinctions among neural stem cells that scientists had thought were the same, MacLellan notes. “There was a lot of divergence in terms of what other people were calling neural stem cells,” he says. Identifying these previously unrecognized subtypes could help scientists better understand the various roles that the cells play in creating new nerve cells for the brain. “This test will help to clarify some of that.”