Abstract
The CNS is thought to develop from self-renewing stem cells that generate neurons, astrocytes, and oligodendrocytes. Other data, however, have suggested that astrocytes and oligodendrocytes are generated from separate progenitor populations. To reconcile these observations, we have prospectively isolated progenitors that do or do not express Olig2, an oligodendrocyte bHLH determination factor. Both Olig2(-) and Olig2(+) progenitors can behave as tripotential CNS stem cells (CNS-SCs) in vitro. Growth in FGF-2 causes induction of Olig2 in the former population, permitting oligodendrocyte differentiation; extinction of Olig2 in the latter cells permits astrocyte differentiation. The induction of Olig2 by FGF-2 is mediated, in part, via endogenous Sonic Hedgehog. These data indicate that clonogenic competence to generate neurons, astrocytes, and oligodendrocytes reflects a deregulation of dorsoventral patterning during expansion in vitro, raising the question of whether such trifatent cells actually exist in vivo.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens / metabolism
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Astrocytes / metabolism
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Basic Helix-Loop-Helix Transcription Factors
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Blotting, Northern
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Body Patterning / physiology*
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Bromodeoxyuridine / metabolism
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Carbocyanines / metabolism
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Cell Aggregation
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Cell Count
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Cell Differentiation / physiology*
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Cells, Cultured
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DNA-Binding Proteins / metabolism
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Dose-Response Relationship, Drug
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Embryo, Mammalian
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Fibroblast Growth Factor 2 / pharmacology
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Fibroblast Growth Factor 2 / physiology*
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Flow Cytometry / methods
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Glial Fibrillary Acidic Protein / metabolism
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Green Fluorescent Proteins
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Hedgehog Proteins
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High Mobility Group Proteins / metabolism
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins / metabolism
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Immunohistochemistry
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In Vitro Techniques
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Luminescent Proteins / metabolism
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Mice
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Nerve Tissue Proteins / metabolism*
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Neurons / metabolism
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O Antigens / metabolism
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / metabolism
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PAX7 Transcription Factor
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Proteoglycans / metabolism
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RNA, Messenger / biosynthesis
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Rats
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Receptor, Platelet-Derived Growth Factor alpha / metabolism
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Reverse Transcriptase Polymerase Chain Reaction / methods
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SOXE Transcription Factors
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Spinal Cord / cytology*
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Spinal Cord / embryology
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Stem Cells / physiology*
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Time Factors
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Trans-Activators / metabolism
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Transcription Factors / metabolism
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Transfection
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Tubulin / metabolism
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Zebrafish Proteins
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beta-Galactosidase / metabolism
Substances
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Antigens
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Basic Helix-Loop-Helix Transcription Factors
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Carbocyanines
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DNA-Binding Proteins
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Enzyme Inhibitors
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Glial Fibrillary Acidic Protein
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Hedgehog Proteins
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High Mobility Group Proteins
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins
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Luminescent Proteins
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Nerve Tissue Proteins
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Nkx6-1 protein, mouse
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Nkx6-1 protein, rat
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O Antigens
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O4 antigen, Stenotrophomonas
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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PAX7 Transcription Factor
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Pax7 protein, mouse
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Proteoglycans
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RNA, Messenger
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SHH protein, human
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SOXE Transcription Factors
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Sox10 protein, mouse
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Sox10 protein, rat
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TO-PRO-3
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Trans-Activators
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Transcription Factors
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Tubulin
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Zebrafish Proteins
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beta3 tubulin, mouse
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chondroitin sulfate proteoglycan 4
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Fibroblast Growth Factor 2
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Green Fluorescent Proteins
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Epidermal Growth Factor
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Receptor, Platelet-Derived Growth Factor alpha
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beta-Galactosidase
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Bromodeoxyuridine