Germ-line immortality

Major advances in stem cell research have occurred over the last decades. Progress has included the generation of lines of human and mouse embryonic stem (ES) cells and the identification and purification of stem cells for multiple independent lineages. Recent studies by Brinster and colleagues in this issue of PNAS (1) also suggest that the reproductive potential of an organism can be prolonged indefinitely by using germ-line stem cells. It even appears that eggs and sperm can develop from cultured mouse ES cells (2–4). Although gametes derived in vitro have yet to prove their developmental potential, these studies suggest that ES cells and germ-line stem cells share many characteristics.

In most mammalian females, meiosis initiates during in utero development, such that no oogenic stem cells exist in the postnatal ovary, thereby limiting the reproductive lifespan of a woman. However, the reproductive lifespan of a man is in theory without limits. Although this reproductive potential of males has long been known, the further characterization and identification of spermatogonial stem cells is only a recent advance.

Three major requirements were needed to advance spermatogonial stem cell research, including (i) an in vivo assay for stem cell function, (ii) knowledge of stem cell markers, and (iii) a method to maintain the stem cells continuously in culture. Similar to his pivotal studies to optimize egg culture and transgenesis (reviewed in refs. 5 and 6), Brinster's group has systematically made giant leaps toward these goals.