Human fetal radial glia cells generate oligodendrocytes in vitro.
Limited knowledge about human oligodendrogenesis prompted us to explore the lineage relationship between cortical radial glia (RG) cells and oligodendrocytes (OLs) in the human fetal forebrain. RG cells were isolated from cortical ventricular/subventricular zone and their progeny was followed in vitro. One portion of RG cells differentiated into cells of OL lineage identified by cell-type specific antibodies, including platelet-derived growth factor receptor-alpha (PDGFRalpha), NG2, O4, myelin basic protein, and myelin oligodendrocyte glycoprotein. Moreover, using Cre Lox fate mapping (brain lipid binding protein-Cre/Floxed-yellow fluorescent protein) we established a direct link between RG cells and OL progenitors. In vitro generation of RG-derived O4(+) OL progenitors was enhanced by addition of sonic hedgehog (SHH) and reduced by the SHH inhibitor, cyclopamine, suggesting the role of SHH signaling in this process. In summary, our in vitro experiments revealed that a portion of cortical RG cells isolated from human forebrain at the second trimester of gestation generates OL progenitors and this suggests a role of SHH in this process.
Mo
Zhicheng
Z
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-3401, USA.
Zecevic
Nada
N
D000941:Antigens / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology*; D010957:Plasmids; D016548:Prosencephalon / Q000166:cytology / Q000196:embryology*; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000072086:Smoothened Receptor; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D014162:Transfection; D014704:Veratrum Alkaloids / Q000494:pharmacology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D053823:Hedgehog Proteins; D008164:Luminescent Proteins; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D011509:Proteoglycans; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014704:Veratrum Alkaloids; D000099216:Chondroitin Sulfate Proteoglycan 4; C571326:MOG protein, human; C509239:SHH protein, human; C491023:SMO protein, human; C000541:cyclopamine