Author/Authors :
Sugiarto، نويسنده , , Sista and Persson، نويسنده , , Anders I. and Munoz، نويسنده , , Elena Gonzalez and Waldhuber، نويسنده , , Markus and Lamagna، نويسنده , , Chrystelle and Andor، نويسنده , , Noemi and Hanecker، نويسنده , , Patrizia and Ayers-Ringler، نويسنده , , Jennifer and Phillips، نويسنده , , Joanna and Siu، نويسنده , , Jason and Lim، نويسنده , , Daniel A. and Vandenberg، نويسنده , , Scott and Stallcup، نويسنده , , William and Berger، نويسنده , , Mitchel S. and Bergers، نويسنده , , Gabriele and Weiss، نويسنده , , William A. and Petritsch، نويسنده , , Claudia، نويسنده ,
Abstract :
Summary
tal 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.
