title: NG2-expressing glial precursor cells are a new potential oligodendroglioma cell initiating population in N-ethyl-N-nitrosourea-induced gliomagenesis.
abstract: Gliomas are the most common primary brain tumor affecting human adults and remain a therapeutic challenge because cells of origin are still unknown. Here, we investigated the cellular origin of low-grade gliomas in a rat model based on transplacental exposure to N-ethyl-N-nitrosourea (ENU). Longitudinal magnetic resonance imaging coupled to immunohistological and immunocytochemical analyses were used to further characterize low-grade rat gliomas at different stages of evolution. We showed that early low-grade gliomas have characteristics of oligodendroglioma-like tumors and exclusively contain NG2-expressing slow dividing precursor cells, which express early markers of oligodendroglial lineage. These tumor-derived precursors failed to fully differentiate into oligodendrocytes and exhibited multipotential abilities in vitro. Moreover, a few glioma NG2+ cells are resistant to radiotherapy and may be responsible for tumor recurrence, frequently observed in humans. Overall, these findings suggest that transformed multipotent NG2 glial precursor cell may be a potential cell of origin in the genesis of rat ENU-induced oligodendroglioma-like tumors. This work may open up new perspectives for understanding biology of human gliomas.
authors.affiliation: INSERM U873, 38054 Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Briançon-Marjollet
authors.forename: Laurent
authors.initials: L
authors.lastname: Balenci
authors.forename: Manuel
authors.initials: M
authors.lastname: Fernandez
authors.forename: François
authors.initials: F
authors.lastname: Estève
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Régine
authors.initials: R
authors.lastname: Farion
authors.forename: Marine
authors.initials: M
authors.lastname: Beaumont
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Barbier
authors.forename: Chantal
authors.initials: C
authors.lastname: Rémy
authors.forename: Jacques
authors.initials: J
authors.lastname: Baudier
mesh_terms: D000818:Animals; D000941:Antigens / Q000032:analysis*; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000473:pathology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005038:Ethylnitrosourea / Q000633:toxicity*; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology*; D009837:Oligodendroglioma / Q000139:chemically induced* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020703:ras GTPase-Activating Proteins / Q000032:analysis; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D005038:Ethylnitrosourea; D011509:Proteoglycans; D020703:ras GTPase-Activating Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C101203:IQ motif containing GTPase activating protein 1