Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain
Choroid plexus-derived miR-204 regulates the number of quiescent neural stem cells in the adult brain
复制标题
DOI：
10.15252/embj.2018100481
复制
发表时间：
2019-07-15
期刊：
影响因子：
11.4
通讯作者：
Ninkovic, Jovica
中科院分区：
文献类型：
--
作者：
Lepko, Tjasa;Pusch, Melanie;Ninkovic, Jovica
成体神经干细胞(NSC)数量的调节对终生神经发生至关重要。在这里，我们确定了一种转录后调控机制，以microRNA204(miR-204)为中心，控制静止的(Q)神经干细胞的维持。MIR-204调控qNSCs中参与细胞周期调控、神经元迁移和分化的一系列转录本。重要的是，抑制miR-204功能减少了室管膜下区(SEZ)中的qNSCs的数量，这是通过诱导NSCs的提前激活和分化而不改变其神经发生潜能来实现的。引人注目的是，我们发现小鼠侧脑室的脉络丛是miR-204的主要来源，miR-204被释放到脑脊液中以控制SEZ内的NSCs的数量。综上所述，我们的结果描述了一种新的机制，通过抑制干细胞的激活和分化来维持成体干细胞。
Regulation of adult neural stem cell (NSC) number is critical for lifelong neurogenesis. Here, we identified a post-transcriptional control mechanism, centered around the microRNA 204 (miR-204), to control the maintenance of quiescent (q)NSCs. miR-204 regulates a spectrum of transcripts involved in cell cycle regulation, neuronal migration, and differentiation in qNSCs. Importantly, inhibition of miR-204 function reduced the number of qNSCs in the subependymal zone (SEZ) by inducing pre-mature activation and differentiation of NSCs without changing their neurogenic potential. Strikingly, we identified the choroid plexus of the mouse lateral ventricle as the major source of miR-204 that is released into the cerebrospinal fluid to control number of NSCs within the SEZ. Taken together, our results describe a novel mechanism to maintain adult somatic stem cells by a niche-specific miRNA repressing activation and differentiation of stem cells.