Studying mice and humans, researchers at Washington University School of Medicine in St. Louis and their collaborators in Paris have identified two proteins that are required to maintain a supply of stem cells in the developing kidney.
In the presence of the two proteins, FGF9 and FGF20, mouse kidney stem cells stayed alive outside the body longer than previously reported. Though the cells were maintained only five days (up from about two), the work is a small step toward the future goal of growing kidney stem cells in the lab.
In the developing embryo, these early stem cells give rise to adult cells called nephrons, the blood filtration units of the kidneys.
The results appear online June 11 in Developmental Cell.
"When we are born, we get a certain allotment of nephrons," says Raphael Kopan, PhD, the Alan A. and Edith L. Wolff Professor of Developmental Biology. "Fortunately, we have a large surplus. We can donate a kidney — give away 50 percent of our nephrons — and still do fine. But, unlike our skin and gut, our kidneys can't build new nephrons."
The skin and the gut have small pools of stem cells that continually renew these organs throughout life. Scientists call such pools of stem cells and their support system a niche. During early development, the embryonic kidney has a stem cell niche as well. But at some point before birth or shortly after, all stem cells in the kidney differentiate to form nephrons, leaving no self-renewing pool of stem cells.
"In other organs, there are cells that specifically form the niche, supporting the stem cells in a protected environment," Kopan says. "But in the embryonic kidney, it seems the stem cells form their own niche, making it a bit more fragile. And the signals and conditions that lead the cells to form this niche have been elusive."
Surprisingly, recent clues to the signals that maintain the embryonic kidney's stem cell niche came from studies of the inner ear. David M. Ornitz, MD, PhD, the Alumni Endowed Professor of Developmental Biology, investigates FGF signaling in mice. Earlier this year, Ornitz and his colleagues published a paper in PLoS Biology showing that FGF20 plays an important role in inner ear development.
"Mice without FGF20 are profoundly deaf," Ornitz says. "While they are otherwise viable and healthy, in some cases we noticed that their kidneys looked small."
Past work from his own lab and others suggested that FGF9, a close chemical cousin of FGF20, might also participate in kidney development. FGF20 and FGF9 are members of a family of proteins known as fibroblast growth factors. In general, members of this family are known to play important and broad roles in embryonic development, tissue maintenance, and wound healing. Mice lacking FGF9 have defects in development of the male urogenital tract and die after birth due to defects in lung development.