Asymmetry-defective oligodendrocyte progenitors are glioma precursors.

in Cancer cell by Sista Sugiarto, Anders I Persson, Elena Gonzalez Munoz, Markus Waldhuber, Chrystelle Lamagna, Noemi Andor, Patrizia Hanecker, Jennifer Ayers-Ringler, Joanna Phillips, Jason Siu, Daniel A Lim, Scott Vandenberg, William Stallcup, Mitchel S Berger, Gabriele Bergers, William A Weiss, Claudia Petritsch

TLDR

  • The study found that a protein called NG2 helps cells called oligodendrocyte progenitor cells (OPC) decide whether to keep renewing themselves or turn into mature cells. The study also found that when NG2 is not divided evenly between the two types of cells, it can lead to the development of cancer.

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.

Overview

  • The study investigates the role of proteoglycan NG2 in the self-renewal and differentiation of postnatal oligodendrocyte progenitor cells (OPC).
  • The study uses mouse models and human cells to examine the asymmetric segregation of NG2 during mitosis and its impact on OPC cell fate and tumor-initiating potential.

Comparative Analysis & Findings

  • The study shows that NG2 segregates asymmetrically during mitosis, with NG2(+) progeny undergoing EGF-dependent proliferation and self-renewal, while NG2(-) progeny differentiates. In a mouse model, decreased NG2 asymmetry is associated with premalignant, abnormal self-renewal and tumor-initiating potential. In human cells, loss of asymmetric division is prevalent in oligodendrogliomas and is associated with the neoplastic transformation of OPC.

Implications and Future Directions

  • The study highlights the importance of NG2 in the regulation of OPC cell fate and tumor-initiating potential. Future research could explore the role of NG2 in other types of cancer and investigate potential therapeutic targets for oligodendrogliomas.
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