Adult neural stem cells differentiate into neurons, astrocytes, and oligodendrocytes in the mammalian CNS, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like grow th factor-I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. However, it is unclear wheth er IGF-I affects multipotent neural stem cells. Here we show that IGF-I stimulates the differentiation of multipotent adult rat hippocampus-derived neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation b y IGF-I appears to be mediated through an inhibition of BMP signaling. Furthermore, overexpression of IGF-I in the hippocampus leads to an increase in oligodendrocyte markers. These data demonstrate the existence of a single molecule, IGF-I, that can influence the fate choice of multipotent adult neural progenitor cells to an oligodendroglial lineage.
IGF-1 INSTRUCTS MULTIPOTENT ADULT CNS NEURAL STEM CELLS TO AN OLIGODENDROGLIAL LINEAGE