How Do Germline Cells Maintain Immortality?

BAR HARBOR, MAINE – Germline stem cells are the cells in our body that give rise to eggs and sperm. They are unique from the rest of the cells in our body because they are the only cells that have immortal potential, or the ability to give rise to each subsequent generation. Researchers in Dr. Dustin Updike’s group at the MDI Biological Laboratory are working to discover what it is that gives germ cells their immortal and stem-cell-like properties. “When cellular immortality is lost, the result is sterility. When improperly acquired, the result is cancer. We’d like to know how cells regulate their immortal potential to make sure it stays on when it is needed, or to turn it off when it is not,” says Updike. Part of the answer resides in special protein and RNA aggregates called germ granules, which are found in the germ cells of all animals. Last year Dr. Updike’s group developed a way to remove these granules from a small worm called C. elegans, an animal used as a model for genetic studies because so many of its genes are shared with humans. What his group found was that removing germ granules causes germ cells to lose their immortal potential, making some to develop as neurons and muscle instead of eggs and sperm.

Anne Campbell, a native of Belfast, Maine, is a Research Assistant in the Updike lab and first author on a paper recently published in Development. Using “next-generation sequencing” techniques, Anne surveyed over 20,000 genes to determine how gene expression changes when germ-granules are lost. She discovered that germ-granules function with another protein called CSR-1 to determine whether germ cells develop as eggs or as sperm. By impairing germ-granule and CSR-1 function, she could switch the fate of developing eggs to make them express sperm genes. These findings provide a better understanding of how germ granules preserve the stem-cell like properties in germ cells, and may eventually improve the safety of patient-derived stem cells that can be used to treat disease.