Tissue cells can revert to stem cells

Scientists at the Carnegie Institution in Baltimore, MD, have found that certain cells involved in egg development in the fruitfly can be stimulated to revert to fully functioning stem cells. “This finding could lead to new sources of stem cells from other tissues and other animals,” commented Dr. Allan Spradling, director of the Carnegie department and co-author of the study published in the March 14 online issue of Nature.

The research conducted by Spradling — a Howard Hughes Medical Institute Investigator — and colleague Dr. Toshie Kai, involved so-called germline stem cells of the female fruitfly. These cells are precursors to eggs and begin their journey as stem cells living in a special environment called a niche. In the niche, a stem cell splits into two daughter cells, one of which leaves the niche to begin its transformation. Through a series of 4 divisions a cluster of 16 cells forms — an immature egg with 15 accompanying nurse cells. The researchers discovered that the cells in clusters of 4 and 8 cells can still return to the stem-cell state under appropriate conditions. Moreover, the reverted stem cells worked as well as normal stem cells. Flies with only reverted stem cells were as fertile as normal flies throughout adult life.

“For most stem cells, it has not been possible yet to determine how quickly their progeny cells lose the ability to function again as stem cells,” Spradling noted. “In the fruitfly (Drosophila) ovary we could directly test this and found conditions where the cluster cells reverted to a stem-cell state and functioned throughout the entire life of the adult. We don’t know yet if this will be a general result that applies to other stem cells,” cautioned Kai. “The progeny of germline stem cells might develop relatively slowly compared with other stem cell progeny, and thus retain their ’stemness’ longer.”

The scientists made their discovery by placing the cell clusters in an unusual environment, the immature ovary of a developing Drosophila larva. “We think that two factors present in the larval ovary may have helped cause the cells to revert back to stem cells,” Kai commented. “First, the larval ovary has an abundant supply of the fruitfly protein that is analogous to a protein (BMP4) involved in germ-cell development in developing mammalian embryos. It is required by fruitfly germline stem cells and maintains them in the niche. Second, the cells in the larval ovary are unlikely to block reversion, in contrast to the cells that cluster cells encounter normally.” Providing the proper conditions for reversion is likely to be a major issue in future attempts to revert differentiating cells back into stem cells.

“Differentiated or partially differentiated cells are much more common in the body than stem cells,” Spradling noted. “So harnessing them could be a valuable strategy in efforts to enhance tissue repair. Some animals that can regenerate lost parts seem to utilize differentiated cells as a source of progenitors, and not just pre-existing stem cells. We are very excited about what further studies in the fruitfly and other animals might show us,” Spradling concluded.