IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle

Secreted peptide growth factors are critical extracellular signals that int eract to promote the proliferation, differentiation, and survival of progen itor cells in developing tissues. IGF-I signaling through the IGF type I re ceptor provides a mitogenic signal for numerous cell types, including stem and progenitor cells. We have utilized the O-2A oligodendrocyte progenitor to study the mechanism of IGF-I mitogenic actions since these progenitors r espond to IGF-I in vitro, and gene targeting studies in mice have demonstra ted that IGF-I is essential for normal oligodendrocyte development in vivo. The goal of this study was to elucidate the mechanism by which IGF-I promo tes the proliferation of oligodendrocyte progenitors in the context of othe r mitogens critical for their proliferation. Results presented here show th at IGF-I significantly amplified the actions of FGF-2 and PDGF to promote D NA synthesis in O-2A progenitors. Investigation of cell cycle kinetics reve aled that IGF-I had no significant effect on the rate of cell cycle progres sion. Instead, IGF-I promoted increased recruitment of O-2A progenitors int o the S phase of the cell cycle. These studies support a role for IGF-I as a cell cycle progression factor for progenitor cells. (C) 2001 Academic Pre ss.