Department of Neurological Surgery, University of California San Francisco, USA.
Cancer Cell. 2011 Sep 13;20(3):328-40. doi: 10.1016/j.ccr.2011.08.011.
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.
少突胶质前体细胞（OPC）在产后自我更新，产生成熟的少突胶质细胞，是少突胶质细胞瘤的细胞来源。我们发现蛋白聚糖 NG2 在有丝分裂期间不对称地分离，从而产生不同命运的 OPC 细胞。NG2 对于 EGFR 向 NG2(+)后代的不对称分离是必需的，后者继而激活 EGFR 并经历 EGF 依赖性增殖和自我更新。相比之下，NG2(-)后代则分化。在小鼠模型中，NG2 不对称性的降低与恶性前体、异常自我更新而不是分化以及肿瘤起始潜能相一致。人 NG2(+)细胞的不对称分裂在非肿瘤组织中很普遍，但在少突胶质细胞瘤中减少。不对称细胞分裂的调节因子在低级别少突胶质细胞瘤中表达错误。我们的结果确定了与 OPC 肿瘤转化相关的不对称分裂的丧失。
