Adult multipotent neural progenitor cells can differentiate 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. However, it is unclear whether IGF-I affects multipotent neural progenitor 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 by IGF-I appears to be mediated through an inhibition of bone morphogenetic protein 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.
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5 January 2004
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January 05 2004
IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes
Jenny Hsieh,
Jenny Hsieh
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
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James B. Aimone,
James B. Aimone
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
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Brian K. Kaspar,
Brian K. Kaspar
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
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Tomoko Kuwabara,
Tomoko Kuwabara
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
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Kinichi Nakashima,
Kinichi Nakashima
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
2Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan
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Fred H. Gage
Fred H. Gage
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
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Jenny Hsieh
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
James B. Aimone
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
Brian K. Kaspar
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
Tomoko Kuwabara
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
Kinichi Nakashima
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
2Department of Cell Fate Modulation, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 860-0811, Japan
Fred H. Gage
1Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037
Address correspondence to Fred H. Gage, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, CA 92037. Tel.: (858) 453-4100. Fax: (858) 597-0824. email: [email protected]
Abbreviations used in this paper: AAV, adeno-associated virus; BMP, bone morphogenetic protein; CNS, central nervous system; IGF, insulin-like growth factor; MBP, myelin basic protein; RA, retinoic acid.
Received:
August 19 2003
Accepted:
November 17 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 164 (1): 111–122.
Article history
Received:
August 19 2003
Accepted:
November 17 2003
Citation
Jenny Hsieh, James B. Aimone, Brian K. Kaspar, Tomoko Kuwabara, Kinichi Nakashima, Fred H. Gage; IGF-I instructs multipotent adult neural progenitor cells to become oligodendrocytes . J Cell Biol 5 January 2004; 164 (1): 111–122. doi: https://doi.org/10.1083/jcb.200308101
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