Stanford Report Online

Stanford Report, October 18, 2000
Stem cells' 'guardians' found to control cell specialization


Scientists at Stanford have discovered what may be a key to understanding how stem cells in the body divide. The discovery could lead to new therapies for replacing defective nerve cells and helping wounds to heal, the researchers said.

Cellular biologists see the cells in our body as part of a great matriarchy: stem cells are the "mother" cells that give rise to all sorts of specialized cells. For instance, all the various kinds of blood cells in our body come from a small population of blood stem cells. When the "mother" cells divide, they generally give rise to two types of "daughter" cells ­ one is the replacement stem cell and the other gives rise to more specialized types of blood cells.

"Stem cell division has to be very tightly regulated," said Margaret Fuller, PhD, professor of developmental biology and of genetics, who led the team making the discovery. Stem cells have the capacity to divide extensively to produce more stem cells, for example during wound healing. Another such time is when stem cells are transplanted into cancer patients who have lost their own blood stem cells due to intense radiation or chemical therapy.

"In transplant patients a small number of stem cells can multiply to fully restore the blood system," Fuller said. However, in the normal case, stem cells do not proliferate to take over the body. Their high capacity for self renewal is instead kept under control and their daughter cells are harnessed to generate differentiated cell types like blood, skin or intestinal epithelial cells.

The research, which was conducted primarily by doctoral student Amy Kiger in Fuller's laboratory, was published last week in the journal Nature. Their study revealed that stem cell reproduction is controlled in part by special surrounding support cells in the body that play a guardian role. These guardian cells send key information that ensures that at least one of the two daughters of a stem cell division differentiates instead of retaining stem cell identity. "Under the influence of the guardian cells, the stem cell divides to produce one stem cell and one specialized cell, rather than two stem cells," Fuller said.

Other scientists had previously hypothesized that surrounding cells might release a factor that prevents specialization of the daughter cells. "Our results show that the opposite is also true," Fuller said. For example, if the previously hypothesized factor were missing, the result would be many specialized daughter cells and the eventual loss of the stem cell population. In contrast, when the factor indicated by Kiger and Fuller's research is missing, the result is too many stem cells.

The effect that Kiger, Fuller and colleagues found is probably only one of many factors that govern the division of stem cells. In the future we may ultimately understand the full complement of factors that control stem cell division, Fuller said.

If scientists do find how to control the division of stem cells, it could have important medical implications. "The long-range goal would be to harness stem cells for treating degenerative disease and to help injuries heal," Fuller said. "Eventually we want to be able to both culture stem cells and induce them to produce specialized cells where and when we want them to."

Kiger and Fuller collaborated on this study with researchers at Oxford University, England, and University of Pennsylvania Medical Center, Philadelphia. The research was supported by a predoctoral fellowship from Howard Hughes Medical Institute to Kiger and by grants from the National Institutes of Health and the National Science Foundation.