Lack of replicative senescence in cultured rat - Oligodendrocyte precursorcells

Most mammalian somatic cells are thought to have a limited proliferative ca pacity because they permanently stop dividing after a finite number of divi sions in culture, a state termed replicative cell senescence. Here we show that most oligodendrocyte precursor cells purified from postnatal rat optic nerve can proliferate indefinitely in serum-free culture if prevented from differentiating; various cell cycle-inhibitory proteins increase, but the cells do not stop dividing. The cells maintain high telomerase activity and p53- and Rb-dependent cell cycle checkpoint responses, and serum or genoto xic drugs induce them to acquire a senescence-like phenotype. Our findings suggest that some normal rodent precursor cells have an unlimited prolifera tive capacity if cultured in conditions that avoid both differentiation and the activation of checkpoint responses that arrest the cell cycle.