Dpp makes multicellular cysts (red, top) dedifferentiate into single cells (bottom).


Germline stem cells (GSCs) on their way to differentiation can change their minds and return to pluripotency, according to Toshie Kai and Allan Spradling (Carnegie Institution of Washington, Baltimore, MD). Such a return is a long-sought goal for those hoping to create pluripotent cells for transplantation.

GSCs in the adult fly reside in a niche where they receive Dpp signals telling them to remain undifferentiated. Upon division, one daughter escapes the niche (and the realm of Dpp) and expresses Bam. The freed cell thus differentiates into a cyst–a set of up to 16 cells interconnected by incomplete cytokinesis and a cytoskeletal structure called the fusome.

Kai and Spradling show that these steps toward differentiation can be undone with Dpp. They overexpressed Dpp in flies to form many GSCs, then induced a transient burst of Bam to produce cysts. Hours later, when Bam was gone, the cysts broke down into single cells resembling GSCs.Using larvae, the group shows that the resulting cells are functional GSCs. As in the adult, transient Bam caused cysts to form, and again these cysts individualized. The resulting single cells developed into normal GSCs as the larvae grew into adults. Reversion of cyst cells may repopulate GSCs depleted by injury or age, for example, although how this choice might be regulated is unknown.

Although other cell types (such as liver) are thought to dedifferentiate on rare occasions, Spradling is excited about the frequency of reversion in cysts. “All the germ cells in the larval ovary become cysts and then, seemingly, all become stem cells again,” he says. So the system should lend itself to finding the factors that direct this backward step. Like cysts, dividing germ cell precursors are transiently linked by a fusome. Spradling wonders whether the severing of this connection is the trigger to stemness. ▪


Kai, T., et al. 2004. Nature. 10.1038/nature02436.