A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States.
A Nuclear Role for miR-9 and Argonaute Proteins in Balancing Quiescent and Activated Neural Stem Cell States.
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DOI：
10.1016/j.celrep.2016.09.088
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发表时间：
2016-10-25
期刊：
影响因子：
8.8
通讯作者：
Coolen M
中科院分区：
文献类型：
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作者：
Katz S;Cussigh D;Urbán N;Blomfield I;Guillemot F;Bally-Cuif L;Coolen M
在整个生命过程中，成体神经干细胞（NSCs）会产生新的神经元和神经胶质，这些神经元和神经胶质有助于重要的大脑功能。静止是成体NSCs的基本保护特征；然而，人们对这种状态的建立和维持仍然知之甚少。我们证明，在成年斑马鱼的皮层中，大脑富集的miR-9仅在静止的NSCs的一个子集中表达，突出了这些细胞内的异质性，并且是维持NSC静止所必需的。引人注目的是，miR-9与Argonaute蛋白（Agos）一起定位于静止的NSCs的细胞核，操纵它们的核/细胞质比例会影响静止。在机制上，miR-9允许有效的Notch信号传导来促进静止，我们鉴定出RISC蛋白TNRC6是miR-9/Agos核在体内定位的中介。我们提出核miR-9/Agos在控制NSC静止和激活之间的平衡中具有保守的非规范作用，这是维持成体生发池的关键步骤。miR-9主要通过允许有效的Notch信号传导来维持NSC的静止，miR-9和Argonaute蛋白存在于成体静止的NSCs的细胞核中，miR-9/Ago的活性核细胞质穿梭影响NSCs的静止状态，成体神经干细胞的基本保护特征是它们的相对静止。Katz等人发现microRNA-9是维持成年NSCs静止的关键因素，并通过非规范的核作用模式在这些细胞内设置异质性。
Throughout life, adult neural stem cells (NSCs) produce new neurons and glia that contribute to crucial brain functions. Quiescence is an essential protective feature of adult NSCs; however, the establishment and maintenance of this state remain poorly understood. We demonstrate that in the adult zebrafish pallium, the brain-enriched miR-9 is expressed exclusively in a subset of quiescent NSCs, highlighting a heterogeneity within these cells, and is necessary to maintain NSC quiescence. Strikingly, miR-9, along with Argonaute proteins (Agos), is localized to the nucleus of quiescent NSCs, and manipulating their nuclear/cytoplasmic ratio impacts quiescence. Mechanistically, miR-9 permits efficient Notch signaling to promote quiescence, and we identify the RISC protein TNRC6 as a mediator of miR-9/Agos nuclear localization in vivo. We propose a conserved non-canonical role for nuclear miR-9/Agos in controlling the balance between NSC quiescence and activation, a key step in maintaining adult germinal pools. miR-9 highlights a state heterogeneity among adult quiescent neural stem cells (NSC) miR-9 maintains NSC quiescence notably through permitting efficient Notch signaling miR-9, along with Argonaute proteins, is present in the nucleus of adult quiescent NSCs Active nucleo-cytoplasmic shuttling of miR-9/Ago impacts NSCs quiescence status An essential protective feature of adult neural stem cells is their relative quiescence. Katz et al. identify microRNA-9 as crucial factor that maintains adult NSCs quiescence and sets a heterogeneity within these cells, through a non-canonical nuclear mode of action.
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DOI：
10.1038/nrg3355
发表时间：
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期刊：
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影响因子：
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影响因子：
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作者：
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影响因子：
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10.1038/nrm3591
发表时间：
2013-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
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