Mitogen and substrate differentially affect the lineage restriction of adult rat subventricular zone neural precursor cell populations

The effects of specific mitogens and substrates on the proliferative capaci ty and the differentiated phenotypic plasticity of neural precursor cell po pulations isolated from the adult rat subventricular zone (SVZ) were examin ed. SVZ cells were grown on uncoated tissue culture plastic, extracellular matrix, or poly-D-ornithine with either laminin or fibronectin. SVZ neural precursor cells could not be generated with platelet-derived growth factor (PDGF), granulocyte macrophage colony stimulating factor, stem cell factor, heparin-binding epidermal growth factor (HB-EGF), granulocyte colony stimu lating factor, or ciliary neurotrophic factor (CNTF), but could be with EGF , fibroblast growth factor 2 (FGF2), and FGF2 plus heparin. Varying combina tions of substrate and mitogen resulted in very different expansion rates a nd/or lineage potential. Neurons, oligodendrocytes, and astrocytes differen tiated from all cultures, but EGF-generated neural precursor cells were mor e restricted to an astrocytic lineage and FGF2-generated neural precursor c ells had a greater capacity for neuronal differentiation. In both EGF- and FGF2-generated cell populations, CNTF increased the number of differentiate d astrocytes, triiodothyronine oligodendrocytes, PDGF neurons, and brain-de rived neurotrophic factor neurons only from EGF cells. Electrophysiological analysis of differentiated cells showed three distinct phenotypes, glial, neuronal, and presumed precursor cells, although the neuronal properties we re immature. Collectively, these data indicate that CNS neural precursor ce ll populations isolated with different mitogens: and substrates are intrins ically different and their characteristics cannot be directly compared. (C) 1999 Academic Press.