To understand how the differentiation of stem cells to oligodendroglial pro
genitors is regulated, we established cultures of neural stem cells from ne
onatal rat striatum in the presence of epidermal growth factor (EGF) as fre
e-floating neurospheres that were then exposed to an increasing amount of B
104 cell-conditioned medium (B104CM). The resultant cells proliferated in r
esponse to B104CM but no longer to EGF. In vitro analysis and transplantati
on studies indicated that these cells were committed to the oligodendroglia
l lineage, and they were thus referred to as oligospheres. Further characte
rization of their expression of early markers, cell cycle, migration, and s
elf-renewal suggests that they were pre-O2A progenitors. RT-PCR analysis in
dicated that the oligosphere cells expressed mRNAs of platelet-derived grow
th factor a receptor in addition to fibroblast growth factor receptor but n
ot EGF receptor; the latter two receptor mRNAs were expressed by neurospher
e cells. Thus, the progression of stem cells to oligodendroglial progenitor
s is likely induced by factors in B104CM.