Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma
Olig2-regulated lineage-restricted pathway controls replication competence in neural stem cells and malignant glioma
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DOI：
10.1016/j.neuron.2007.01.009
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发表时间：
2007-02-15
期刊：
影响因子：
16.2
通讯作者：
Rowitch, David H.
中科院分区：
文献类型：
--
作者：
Ligon, Keith L.;Huillard, Emmanuelle;Rowitch, David H.
最近的研究发现了脑癌中的干细胞。然而，它们与正常中枢神经系统祖细胞的关系，包括对共同谱系限制途径的依赖，尚不清楚。我们观察到中枢神经系统限制性转录因子 OLIG2 在人胶质瘤干细胞和祖细胞中的表达，让人想起成人大脑生发区的 C 型转运放大细胞。在遗传相关的小鼠模型中，Olig2 功能是神经祖细胞增殖和神经胶质瘤形成所必需的。此外，我们发现 p21(WAF1/CIP1)（一种肿瘤抑制因子和干细胞增殖抑制剂）在神经祖细胞和神经胶质瘤中被 OLIG2 直接抑制。我们的研究结果确定了 Olig2 调节的谱系限制途径，对于正常和致瘤中枢神经系统干细胞的增殖至关重要。
Recent studies have identified stem cells in brain cancer. However, their relationship to normal CNS progenitors, including dependence on common lineage-restricted pathways, is unclear. We observe expression of the CNS-restricted transcription factor, OLIG2, in human glioma stem and progenitor cells reminiscent of type C transit-amplifying cells in germinal zones of the adult brain. Olig2 function is required for proliferation of neural progenitors and for glioma formation in a genetically relevant murine model. Moreover, we show p21(WAF1/CIP1), a tumor suppressor and inhibitor of stem cell proliferation, is directly repressed by OLIG2 in neural progenitors and gliomas. Our findings identify an Olig2-regulated lineage-restricted pathway critical for proliferation of normal and tumorigenic CNS stem cells.