OLIGODENDROBLASTS DISTINGUISHED FROM O-2A GLIAL PROGENITORS BY SURFACE PHENOTYPE (O4(-)) AND RESPONSE TO CYTOKINES USING SIGNAL TRANSDUCER LIFR-BETA()GALC()

The developmental potential of progenitors at two final stages of the macroglial lineage giving rise to oligodendrocytes in postnatal rat br ain was studied in response to defined and serum inducers of astrocyte gene expression. Cell immunoselection [with G(D3) ganglioside, O4 and galactocerebroside (GalC) antibodies] was used to isolate G(D3)(+)O4( -) and O4(+)GalC(-) phenotypes directly from premyelinating cerebrum. In a basal defined culture medium, G(D3)(+)O4(-) progenitors different iated infrequently into oligodendrocytes on a growth substratum compri sed of meningeal cell-derived extracellular matrix. Their conversion i nto astrocytes, as determined by immunofluorescence analysis of glial fibrillary acidic protein expression, was induced by oncostatin-M as w ell as leukemia inhibitory factor (LIF) and ciliary neurotrophic facto r, but not interleukin-6, and required extracellular matrix. By compar ison, O4(+)GalC(-) progenitors were refractory to astrocyte induction under these conditions, as in short-term cultures of optic nerve, and differentiated into myelinogenic oligodendrocytes instead. Only in res ponse to an overriding stimulus in fetal bovine serum did O4(+)GalC(-) progenitors, like their immediate precursors, become astrocytic. Thes e data functionally distinguish two classes of astrocyte-inducing agen ts to provide clear evidence of an oligodendroblast, a progenitor defi ned by surface phenotype (O4(+)GalC(-)) and an altered response of the oligodendrocyte lineage to cytokines using signal transducer LIFR bet a. (C) 1995 Academic Press, Inc.