Fruit flies, or Drosophila, have a long and illustrious history as laboratory guinea pigs. Now it turns out these lowly lab creatures are challenging one of the basic paradigms of stem cell research, that being the belief that the ability to form new cell types or tissues diminishes as a cell becomes more specialized.
Researcher Molly Weaver was simply investigating how the respiratory system of the fly is remodeled when the animal transforms from a tiny, grub-like larva into a full-fledged, winged fly lusting after bananas and apples. What she found was a surprise: Specialized cells, she determined, naturally regress to serve as a kind of de facto stem cell during the fruit-fly life cycle.
“It was mind-boggling, because it went completely against what we had expected to see happening,” said Ms. Weaver, PhD. “Once we figured out what was happening, however, the results were very clear.” Weaver is a postdoctoral scholar in the laboratory of Mark Krasnow, MD, PhD, professor and chair of biochemistry.
Weaver and Krasnow, who is also a Howard Hughes Medical Institute investigator, wanted to know what happened to the tracheal system during the fly’s switch from squirmer to hoverer. They looked at fruit flies genetically modified so that proliferating cells in the trachea expressed a highly visible green fluorescent protein. This allowed the researchers to track the fate and location of the cells by looking for those that glowed green under a microscope.
As they did so things got interesting fast. Although the trachea branch from either side of the dorsal trunk, only one side has imaginal cells. The expectation has always been that these cells migrate across the dorsal trunk to repopulate both sides of the trachea with a flying-appropriate blend of cell types. But, despite spending countless hours behind a microscope, Weaver never saw any green cells making their way to the other side.
“I had about four different hypotheses to explain why I couldn’t see any of these cells crossing the dorsal trunk,” said Weaver. “It took quite a while to convince ourselves what was truly going on.”
Further experiments following the fate of individual stalk cells in live fruit flies proved that a group of well-differentiated cells known as the anterior dorsal branch stalk cells were actually stepping in to repopulate the side of the trachea lacking imaginal cells. As a result, the researchers concluded that a single tissue was being remodeled by two types of multipotent cells: one, the undifferentiated imaginal cells held in reserve to repopulate the fruit fly body, and the other, a highly specialized cell that reverses its developmental course in order to give rise to different cell types.
“To find two very different kinds of progenitor cells in a single fruit-fly tissue raises the possibility that there may be more than one kind of adult stem cell in mammalian tissue,” said Krasnow. “It may be that organisms use both quiescent, undifferentiated cells and more highly differentiated yet reversible facultative (existing under some conditions but not others) stem cells under different conditions.”
Harnessing this type of developmental backtracking in adult human cells would allow researchers to explore new avenues for treating many human diseases. Although recent research has shown that human skin cells can be coaxed in a laboratory dish to generate many other types of cells, the conversion currently requires the use of viruses to deliver specific combinations of genes into the cells. The existence in humans of similar, naturally occurring stem cell understudies, called “facultative stem cells,” has recently been proposed, but the idea remains controversial.
Adapted from the Stanford University announcement.