Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis
Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis
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DOI：
10.1016/j.stem.2020.01.002
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发表时间：
2020-02-06
期刊：
影响因子：
23.9
通讯作者：
Goetz, Magdalena
中科院分区：
文献类型：
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作者：
Kjell, Jacob;Fischer-Sternjak, Judith;Goetz, Magdalena
哺乳动物的大脑中几乎没有能够产生新神经元的神经干细胞（NSC）的小生境，而其他区域主要是胶质细胞。在这里，我们利用室管膜下区NSC龛和嗅球的空间分离，室管膜下区新产生的神经元迁移和整合的区域，并提出了一个全面的蛋白质组学表征这些区域相比，大脑皮层，这是不利于神经发生和新神经元的整合。我们发现不同的组合物的调节细胞外基质（ECM）成分的神经原性龛。我们进一步表明，静止的神经干细胞是其本地ECM的主要来源，包括多功能酶转氨酶2，我们表明这是至关重要的神经发生。原子力显微镜证实的迹象，从蛋白质组学分析，神经原性壁龛显着比非神经原性薄壁组织僵硬。这些发现为揭示神经原性小生境的独特组成提供了强大的资源。
The mammalian brain contains few niches for neural stem cells (NSCs) capable of generating new neurons, whereas other regions are primarily gliogenic. Here we leverage the spatial separation of the sub-ependymal zone NSC niche and the olfactory bulb, the region to which newly generated neurons from the sub-ependymal zone migrate and integrate, and present a comprehensive proteomic characterization of these regions in comparison to the cerebral cortex, which is not conducive to neurogenesis and integration of new neurons. We find differing compositions of regulatory extracellular matrix (ECM) components in the neurogenic niche. We further show that quiescent NSCs are the main source of their local ECM, including the multi-functional enzyme transglutaminase 2, which we show is crucial for neurogenesis. Atomic force microscopy corroborated indications from the proteomic analyses that neurogenic niches are significantly stiffer than non-neurogenic parenchyma. Together these findings provide a powerful resource for unraveling unique compositions of neurogenic niches.