INVITRO ANALYSIS OF THE ORIGIN AND MAINTENANCE OF O-2AADULT PROGENITOR CELLS

We have been studying the differing characteristics of oligodendrocyte-type-2 astrocyte (O-2A) progenitors isolated from optic nerves of perinatal and adult rats. These two cell types display striking differences in their in vitro phenotypes. In addition, the O-2A(perinatal) progenitor population appears to have a limited life-span in vivo, while O-2A(adult) progenitors appear to be maintained throughout life. O-2A(perinatal) progenitors seem to have largely disappeared from the optic nerve by 1 mo after birth, and are not detectable in cultures derived from optic nerves of adult rats. In contrast, O-2A(adult) progenitors can first be isolated from optic nerves of 7-d-old rats and are still present in optic nerves of 1-yr-old rats. These observations raise two questions: (a) From what source do O-2A(adult) progenitors originate; and (b) how is the O-2A(adult) progenitor population maintained in the nerve throughout life? We now provide in vitro evidence indicating that O-2A(adult) progenitors are derived directly from a subpopulation of O-2A(perinatal) progenitors. We also provide evidence indicating that O-2A(adult) progenitors are capable of prolonged self renewal in vitro. In addition, our data suggests that the in vitro generation of oligodendrocytes from O-2A(adult) progenitors occurs primarily through asymmetric division and differentiation, in contrast with the self-extinguishing pattern of symmetric division and differentiation displayed by O-2A(perinatal) progenitors in vitro. We suggest that O-2A(adult) progenitors express at least some properties of stem cells and thus may be able to support the generation of both differentiated progeny cells as well as their own continued replenishment throughout adult life.