Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signaling.
Glioblastoma stem cells induce quiescence in surrounding neural stem cells via Notch signaling.
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DOI：
10.1101/gad.336917.120
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发表时间：
2020-12-01
影响因子：
10.5
通讯作者：
Rodríguez TA
中科院分区：
文献类型：
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作者：
Lawlor K;Marques-Torrejon MA;Dharmalingham G;El-Azhar Y;Schneider MD;Pollard SM;Rodríguez TA
在劳勒等人的这项研究中，作者试图了解胶质母细胞瘤的起源细胞，并分析了从成年小鼠室下区壁龛分离的转化和野生型神经干细胞(NSCs)之间的相互作用。他们的发现表明，致癌基因突变不仅通过细胞固有优势在干细胞利基中传播，而且通过抑制邻近干细胞的增殖而与邻近干细胞竞争。越来越多的证据表明，成人神经干细胞(NSCs)是胶质母细胞瘤的起源细胞。在这里，我们分析了从成年小鼠室下区巢分离出的转化和野生型神经干细胞之间的相互作用。我们发现，转化后的神经干细胞对静止诱导的信号不敏感。出乎意料的是，我们还证明了这些细胞以细胞-细胞接触和Notch信号依赖的方式诱导周围野生型NSCs静止。因此，我们的发现表明，致癌基因突变不仅通过细胞固有优势在干细胞利基中传播，而且通过抑制邻近干细胞的增殖而胜过邻近干细胞。
In this study from Lawlor et al., the authors sought to understand the cell of origin for glioblastoma, and analyzed the interaction between transformed and wild-type neural stem cells (NSCs) isolated from the adult mouse subventricular zone niche. Their findings suggest that oncogenic mutations are propagated in the stem cell niche not just through cell-intrinsic advantages, but also by outcompeting neighboring stem cells through repression of their proliferation. There is increasing evidence demonstrating that adult neural stem cells (NSCs) are a cell of origin of glioblastoma. Here we analyzed the interaction between transformed and wild-type NSCs isolated from the adult mouse subventricular zone niche. We found that transformed NSCs are refractory to quiescence-inducing signals. Unexpectedly, we also demonstrated that these cells induce quiescence in surrounding wild-type NSCs in a cell–cell contact and Notch signaling-dependent manner. Our findings therefore suggest that oncogenic mutations are propagated in the stem cell niche not just through cell-intrinsic advantages, but also by outcompeting neighboring stem cells through repression of their proliferation.
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