Stem cells give rise to all of the cells in an organism’s body. They have the unique ability to produce cells that differentiate into specialized structures, such as tissue and bone, and create new stem cells to replenish the stem cell population. Scientists have long been investigating the mechanisms that allow these special cells to perform this unmatched double duty.
Studying the common fruit fly Drosophila, Erika Matunis and Natalia Tulina of the Department of Embryology at the Carnegie Institution of Washington, have identified a key gene that initiates the signaling process that instructs a stem cell to renew itself instead of differentiating into another type of cell. Their results are published in today's issue of Science.
The Carnegie researchers study the stem cells that lead to sperm in the fruit fly. These stem cells attach to a niche called the hub, which consists of a cluster of support cells in the Drosophila 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, researchers identified genes that are needed for stem cells to produce differentiating cells (see Nature 407, p. 754). In the Carnegie study, the investigators searched for an opposing signal that is responsible for instructing stem cells to self-renew.
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 to change 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, resulting in the expression of stem cell-specific genes. In contrast, cells distant from the hub do not receive enough Unpaired to activate STAT, and instead they 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 that program stem cell self-renewal in more complex organisms.”
After identifying the Upd gene as the first step in the complicated signaling process, the researchers turned their attention to determining whether Upd instructs a stem cell to self-renew or simply maintain viability. They found that, in fact, the cascade of signaling events promotes the self-renewal of these unique cells.
[Contact: Tina McDowell]
21-Dec-2001
