Deregulation of dorsoventral patterning by FGF confers trilineage differentiation capacity on CNS stem cells in vitro.
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.
Gabay
Limor
L
Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.
Lowell
Sally
S
Rubin
Lee L
LL
Anderson
David J
DJ
D000818:Animals; D000941:Antigens / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D015152:Blotting, Northern; D019521:Body Patterning / Q000502:physiology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D002449:Cell Aggregation; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D005434:Flow Cytometry / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins / Q000378:metabolism; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D019081:O Antigens / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism; D051763:PAX7 Transcription Factor; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D055757:SOXE Transcription Factors; D013116:Spinal Cord / Q000166:cytology* / Q000196:embryology; D013234:Stem Cells / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014404:Tubulin / Q000378:metabolism; D029961:Zebrafish Proteins; D001616:beta-Galactosidase / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D002232:Carbocyanines; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D016222:Fibroblast Growth Factor 2; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D006609:High Mobility Group Proteins; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D019081:O Antigens; D000076104:Oligodendrocyte Transcription Factor 2; D051763:PAX7 Transcription Factor; D011509:Proteoglycans; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D055757:SOXE Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D014404:Tubulin; D029961:Zebrafish Proteins; D001616:beta-Galactosidase; D000099216:Chondroitin Sulfate Proteoglycan 4; C491328:Nkx6-1 protein, mouse; C491327:Nkx6-1 protein, rat; C430944:O4 antigen, Stenotrophomonas; C512773:Olig2 protein, mouse; C497322:Pax7 protein, mouse; C509239:SHH protein, human; C527924:Sox10 protein, mouse; C527925:Sox10 protein, rat; C098830:TO-PRO-3; C462941:beta3 tubulin, mouse