Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche.
Distinct Requirements for Extracellular and Intracellular MMP12 in the Development of the Adult V-SVZ Neural Stem Cell Niche.
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DOI：
10.1016/j.stemcr.2018.01.038
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发表时间：
2018-03-13
影响因子：
5.9
通讯作者：
Colognato H
中科院分区：
文献类型：
--
作者：
Shan X;Tomlinson L;Yang Q;Colognato H
成人室-室下区(V-SVZ)干细胞壁龛中神经干细胞(NSC)激活的调控机制一直是深入研究的焦点，但该壁龛最初是如何发展和组织的却鲜为人知。在这里，我们研究了基质金属蛋白酶(MMPs)在V-SVZ干细胞生态位发展中的潜在作用。研究发现，MMP12能促进合适的壁龛细胞排列，形成专门的壁龛细胞外基质，以及包围和支持壁龛神经干细胞的室管膜细胞的平移平面细胞极性。令人惊讶的是，室管膜细胞被发现有一个细胞内MMP12池，通过上调FOXJ1促进室管膜细胞纤毛发生。此外，细胞外和细胞内的MMP12都通过促进NSC的静止来调节V-SVZ的生态位输出。这些发现表明，细胞外和细胞内的MMP12都具有独特和重叠的作用，有助于协调成人V-SVZ干细胞生态位的发展。细胞外和细胞内MMP12在V-SVZ干细胞壁龛中的作用细胞外MMP12促进细胞和细胞外V-SVZ壁龛组织细胞内MMP12足以促进室管膜FOXJ1和纤毛的发生，两者形成的MMP12抑制V-SVZ神经干细胞的增殖。有报道称，基质金属蛋白酶12(MMP12)对V-SVZ神经干细胞生态位的适当发育是必需的，分泌的MMP12促进了生态位的组织和功能，包括调节神经干细胞的静止。一个意想不到的细胞内池的截短但功能的MMP12也被发现，它在促进室管膜纤毛发生方面具有明显的作用。
The regulatory mechanisms that control neural stem cell (NSC) activation in the adult ventricular-subventricular zone (V-SVZ) stem cell niche have been the focus of intense investigation, yet how the niche first develops and organizes is poorly understood. Here, we examined matrix metalloproteinases (MMPs) for potential roles in V-SVZ stem cell niche development. MMP12 was found to promote appropriate niche cellular arrangements, the formation of specialized niche extracellular matrix, and the translational planar cell polarity of ependymal cells that surround and support niche NSCs. Surprisingly, ependymal cells were found to have an intracellular pool of MMP12 that promoted ependymal cell ciliogenesis by upregulating FOXJ1. In addition, both extracellular and intracellular MMP12 were found to regulate V-SVZ niche output by promoting NSC quiescence. These findings reveal that extracellular and intracellular MMP12 have both unique and overlapping roles that help orchestrate the development of the adult V-SVZ stem cell niche. Both extracellular and intracellular MMP12 function in the V-SVZ stem cell niche Extracellular MMP12 promotes cellular and extracellular V-SVZ niche organization Intracellular MMP12 is sufficient to enhance ependymal FOXJ1 and ciliogenesis Both MMP12 forms suppress V-SVZ neural stem cell proliferation Shan et al. report that matrix metalloproteinase 12 (MMP12) is required for the appropriate development of the V-SVZ neural stem cell niche, with secreted MMP12 promoting niche organization and function, including the regulation of neural stem cell quiescence. An unexpected intracellular pool of a truncated yet functional MMP12 was also identified, which has a distinct role in promoting ependymal ciliogenesis.
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影响因子：
6.2
作者：
Relucio J;Menezes MJ;Miyagoe-Suzuki Y;Takeda S;Colognato H
通讯作者：
Colognato H
影响因子：
12.4
作者：
Ostrowski, LE;Hutchins, JR;O'Neal, WK
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影响因子：
64.8
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影响因子：
4.6
作者：
Jacquet, Benoit V.;Salinas-Mondragon, Raul;Ghashghaei, H. Troy
通讯作者：
Ghashghaei, H. Troy
影响因子：
5.3
作者：
Larsen, PH;DaSilva, AG;Yong, VW
通讯作者：
Yong, VW