No individual organism lives forever, but its genes and traits may be passed along from generation to generation thanks to its germ cells. Germ cells are the progenitors of sperm and eggs, and the ability of any species to perpetuate itself depends on the ability of its germ cells to give rise to all the cells of each subsequent generation. That ability – the capacity of a cell to become, by dividing and differentiating, any and all parts of a given organism, including the next generation of germ cells – is called “totipotency.” It’s an extraordinary property that essentially confers immortality on germ cells.
What makes germ cells totipotent? My lab studies small aggregates called “germ granules” that are found just outside the nucleus of germ cells. Recent research has shown that germ granules play a critical role in maintaining the totipotent and immortal properties of the germ cell line. Take away an organism’s germ granules, and it becomes sterile. Find a way to add them to non-germ or “somatic” cells in some organisms, and those cells become fertile germ or stem-like cells.
Germ granules may help keep germ cells from growing into more specific cell types, in which case learning how they apply those particular brakes may help us control cancer. Germ cells may also hold some of the keys to understanding the process of aging, since to perpetuate the species, an organism’s germ cells must resist the effects of aging and of stressors within the environment. So we are studying the role germ granules may play in avoiding senescence.
* * * * * * * * * * * * * * * * * * * * * * * * *
The emerging field of regenerative medicine requires an understanding of the developmental potential of stem cells and the mechanisms by which they can be regulated. During development, non-reproductive cells of an organism display ever more restricted developmental potential as they lose their pluripotency and differentiate into mature tissues, a process that must be reversed to create regenerative stem cells. In contrast to non-reproductive cells, reproductive or germline cells must retain their pluripotency so they can give rise to all of the cell types of each subsequent generation. The pluripotent and self-renewing properties of germ cells rely, in part, on small cellular aggregates called germ granules, which are found in the germline cytoplasm from worms to humans. The loss of germ granules results in sterility; conversely, their presence is sufficient in some species to transform non-reproductive cells into fertile germ cells.
Our lab uses the small roundworm C. elegans as a genetic model to understand germ granule function across species. Using these worms, we are able to determine the genetic components responsible for germ granule assembly and localization, their biophysical properties, and how they function in germ cells. Because germ granules play a role in cellular self-renewal and pluripotency, germ granule research not only impacts the field of reproductive biology, but will also add a new dimension to ongoing efforts in the field of regenerative medicine.