Regulation of neuronal differentiation in human CNS stem cell progeny by leukemia inhibitory factor

The generation of diverse types of neural cells during development occurs t hrough the progressive restriction of the fate potential of neuroepithelial progenitor cells. This process is controlled by factors intrinsic and extr insic to the cell. While the effect of extrinsic cues on multipotent stem c ells of the murine central nervous system (CNS) is becoming clearer, little is known of neural stem cells of human origin. We sought to establish the roles played by two cytokines, leukemia inhibitory (LIF) and ciliary neurot rophic factor (CNTF), and by nerve growth factor (NGF) and platelet-derived growth factor (PDGF) in regulating neuronal and astroglial differentiation in cultured embryonic diencephalic human stem cells. While NGF did not inf luence either neuronal or glial formation, PDGF surprisingly decreased the percentage of stem cell-generated neurons, an effect opposite to that obser ved in murine progenitors. Furthermore, while we confirmed the known abilit y of LIF and CNTF to support astroglial differentiation, we also observed t hat, in contrast with their murine counterparts, the fraction of CNS stem c ell-generated neurons in human cultures was enhanced twofold in the presenc e of both cytokines. These findings highlight important differences between humans and rodents in regard to the way epigenetic cues regulate the funct ion of neural stem cells. Copyright (C) 2000 S. Karger AG. Basel.