Quiescence and Activation of Stem and Precursor Cell Populations in the Subependymal Zone of the Mammalian Brain Are Associated with Distinct Cellular and Extracellular Matrix Signals
Quiescence and Activation of Stem and Precursor Cell Populations in the Subependymal Zone of the Mammalian Brain Are Associated with Distinct Cellular and Extracellular Matrix Signals
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DOI：
10.1523/jneurosci.0700-10.2010
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发表时间：
2010-07-21
影响因子：
5.3
通讯作者：
Ffrench-Constant, Charles
中科院分区：
文献类型：
--
作者：
Kazanis, Ilias;Lathia, Justin D.;Ffrench-Constant, Charles
侧脑室室管膜下区(SEZ)是成人大脑中神经干细胞(NSCs)通过快速分裂的前体不断产生新神经元的区域之一。这个神经源性的生态位是一个复杂的细胞和细胞外微环境，与非神经源性脑室周围区域相比，它具有高度的血管化，在其中NSCs和前体表现出不同的行为。在这里，我们研究了细胞外基质分子及其受体调节这种差异行为的可能机制。我们发现，神经干细胞和前体细胞在成年雄性小鼠的SEZ内通过相同的区域进行有丝分裂--尽管NSCs更接近室管膜细胞--并且与脑室的距离比与血管的距离是神经源性活动的更强的限制因素。此外，我们发现神经干细胞和前体细胞嵌入了富含层粘连蛋白的细胞外基质中，它们都可以对细胞外基质做出贡献。重要的是，它们表达不同水平的细胞外基质受体，神经干细胞表达低水平的α6β1整合素、Syndecan-1和路德教，在体内阻断β1整合素选择性地诱导前体细胞的增殖和异位迁移。最后，当神经干细胞在前体耗尽后被激活以重建生态位时，层粘连蛋白受体的表达上调。这些结果表明，成年神经干细胞及其前体的不同行为并不一定是通过暴露于不同的细胞外信号来调节的，而是通过它们与微环境相互作用的内在调节来调节的。
The subependymal zone (SEZ) of the lateral ventricles is one of the areas of the adult brain where new neurons are continuously generated from neural stem cells (NSCs), via rapidly dividing precursors. This neurogenic niche is a complex cellular and extracellular microenvironment, highly vascularized compared to non-neurogenic periventricular areas, within which NSCs and precursors exhibit distinct behavior. Here, we investigate the possible mechanisms by which extracellular matrix molecules and their receptors might regulate this differential behavior. We show that NSCs and precursors proceed through mitosis in the same domains within the SEZ of adult male mice-albeit with NSCs nearer ependymal cells-and that distance from the ventricle is a stronger limiting factor for neurogenic activity than distance from blood vessels. Furthermore, we show that NSCs and precursors are embedded in a laminin-rich extracellular matrix, to which they can both contribute. Importantly, they express differential levels of extracellular matrix receptors, withNSCsexpressing low levels of alpha 6 beta 1 integrin, syndecan-1, and lutheran, and in vivo blocking of beta 1 integrin selectively induced the proliferation and ectopic migration of precursors. Finally, when NSCs are activated to reconstitute the niche after depletion of precursors, expression of laminin receptors is upregulated. These results indicate that the distinct behavior of adult NSCs and precursors is not necessarily regulated via exposure to differential extracellular signals, but rather via intrinsic regulation of their interaction with their microenvironment.