title: Asymmetry-defective oligodendrocyte progenitors are glioma precursors.
abstract: Postnatal oligodendrocyte progenitor cells (OPC) self-renew, generate mature oligodendrocytes, and are a cellular origin of oligodendrogliomas. We show that the proteoglycan NG2 segregates asymmetrically during mitosis to generate OPC cells of distinct fate. NG2 is required for asymmetric segregation of EGFR to the NG2(+) progeny, which consequently activates EGFR and undergoes EGF-dependent proliferation and self-renewal. In contrast, the NG2(-) progeny differentiates. In a mouse model, decreased NG2 asymmetry coincides with premalignant, abnormal self-renewal rather than differentiation and with tumor-initiating potential. Asymmetric division of human NG2(+) cells is prevalent in non-neoplastic tissue but is decreased in oligodendrogliomas. Regulators of asymmetric cell division are misexpressed in low-grade oligodendrogliomas. Our results identify loss of asymmetric division associated with the neoplastic transformation of OPC.
authors: Department of Neurological Surgery, University of California San Francisco, USA.
authors: Sista
authors: S
authors: Sugiarto
authors: Anders I
authors: AI
authors: Persson
authors: Elena Gonzalez
authors: EG
authors: Munoz
authors: Markus
authors: M
authors: Waldhuber
authors: Chrystelle
authors: C
authors: Lamagna
authors: Noemi
authors: N
authors: Andor
authors: Patrizia
authors: P
authors: Hanecker
authors: Jennifer
authors: J
authors: Ayers-Ringler
authors: Joanna
authors: J
authors: Phillips
authors: Jason
authors: J
authors: Siu
authors: Daniel A
authors: DA
authors: Lim
authors: Scott
authors: S
authors: Vandenberg
authors: William
authors: W
authors: Stallcup
authors: Mitchel S
authors: MS
authors: Berger
authors: Gabriele
authors: G
authors: Bergers
authors: William A
authors: WA
authors: Weiss
authors: Claudia
authors: C
authors: Petritsch
mesh_terms: D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D001921:Brain; D002454:Cell Differentiation; D002455:Cell Division; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D009837:Oligodendroglioma / Q000473:pathology*; D011509:Proteoglycans / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D066246:ErbB Receptors; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4