Stem cells give rise to all the cells in an organism’s body. They can both produce cells that differentiate into specialized structures, such as tissue and bone, and create new stem cells that replenish the stem cell population. But how these cells perform this double duty continues to elude science.
Through the work of Erika Matunis and Natalia Tulina at the Department of Embryology, researchers are now one step closer to unlocking the mechanisms that give stem cells their unique abilities. By studying the stem cells that lead to sperm in the fruit fly Drosophila, the two have been able to identify a key gene that initiates the signaling process instructing a stem cell to renew itself instead of differentiating into another type of cell. Their results were published in the December 21, 2001, issue of Science.
Fruit-fly stem cells attach to a niche called the hub, which consists of a cluster of support cells in the testes. Upon cell division, some of the cells move away from the hub and differentiate into sperm, while others stay near the hub and remain stem cells. Recently other researchers identified genes that are needed for stem cells to produce differentiating cells. The Carnegie investigators searched for an opposing signal that is responsible for instructing stem cells to renew themselves. They found that a gene called unpaired (upd) is expressed in hub cells and that it activates a cascade of signals in a signaling pathway known as Jak-STAT, which promotes self-renewal.
The Jak-STAT signaling pathway was first identified in humans. When this pathway is activated, the STAT transcription factor—a gene that controls the transcription of other genes—binds to target genes and changes the cell’s pattern of gene expression. The researchers think that cells closest to the hub receive high enough levels of unpaired to activate STAT and that this results in the expression of stem cell–specific genes. Cells distant from the hub, in contrast, do not receive enough unpaired to activate STAT, and they instead differentiate. According to Matunis, “The fact that all organisms have so many genes in common suggests that the identification of the unpaired gene’s function will help others find similar genes programming stem cell self-renewal in more complex organisms.”
 Photo Courtesy Erika Matunis |