multipotent neural prgenitor cells to become oligodendrocytes

Multipotent neural prgenitor cells to become oligodendrocytes

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The Journal of Cell Biology The Rockefeller University Press, 0021-9525/2004/01/111/12 $8.00 The Journal of Cell Biology, Volume 164, Number 1, January 5, 2004 111–122 http://www.jcb.org/cgi/doi/10.1083/jcb.200308101 JCB Article 111 IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes Jenny Hsieh, 1 James B. Aimone, 1 Brian K. Kaspar, 1 Tomoko Kuwabara, 1 Kinichi Nakashima, 1,2 and Fred H. Gage 1 1 Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037 2 Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan dult multipotent neural progenitor cells can differ- entiate into neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system, but the molecular mechanisms that control their differentiation are not yet well understood. Insulin-like growth factor I (IGF-I) can promote the differentiation of cells already committed to an oligodendroglial lineage during development. How- ever, it is unclear whether IGF-I affects multipotent neural progenitor cells. Here, we show that IGF-I stimulates the dif- ferentiation of multipotent adult rat hippocampus-derived A neural progenitor cells into oligodendrocytes. Modeling analysis indicates that the actions of IGF-I are instructive. Oligodendrocyte differentiation by IGF-I appears to be me- diated through an inhibition of bone morphogenetic protein signaling. Furthermore, overexpression of IGF-I in the hip- pocampus leads to an increase in oligodendrocyte mark- ers. 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 oligoden- droglial lineage. Introduction Multipotent cells with the ability to divide and differentiate have been shown to exist throughout the central nervous system (CNS), yet neurogenesis appears to be restricted to two specific brain regions within the adult CNS: the subven- tricular zone and the hippocampal subgranular zone (Gage, 2000). Beyond these two regions, most of the dividing cells in other areas give rise to new glial cells and not neurons (Horner et al., 2000; Kornack and Rakic, 2001; Rakic, 2002). However, when these dividing cells are isolated from different regions of the CNS (Reynolds and Weiss, 1992; Lois and Alvarez-Buylla, 1993; Palmer et al., 1997), including nonneurogenic areas (Shihabuddin et al., 1997; Palmer et al., 1999; Kondo and Raff, 2000), they all retain the ability to self-renew and differentiate into neurons, oligodendrocytes, and astrocytes in culture. Remarkably, even proliferating cells isolated from nonneurogenic areas can differentiate into neurons when transplanted back into the hippocampus (Suhonen et al., 1996; Shihabuddin et al., 2000), suggesting that cues from the local environment influence their fate determination and differentiation programs.
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Multipotent neural prgenitor cells to become oligodendrocytes

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