Gao Zhengliang, Ding Peiguo, Hsieh Jenny
Department of Molecular Biology, UT Southwestern Medical Center Dallas, TX, USA.
Front Neurosci. 2012 May 10;6:67. doi: 10.3389/fnins.2012.00067. eCollection 2012.
Multipotent neural stem cells (NSCs) possess the ability to self-renew and differentiate into both neurons and glia. However, the detailed mechanisms underlying NSC fate decisions are not well understood. Recent work suggests that the interaction between cell type specific transcription factors and microRNAs (miRNAs) is important as resident neural stem/progenitor cells give rise to functionally mature neurons. Recently, we demonstrated that the transcriptional repressor REST (RE1-silencing transcription factor) is essential to prevent precocious neuronal differentiation and maintain NSC self-renewal in the adult hippocampus. Here we show that REST is required for orchestrating the expression of distinct subsets of miRNAs in primary mouse NSC cultures, a physiologically relevant cell type. Using miRNA array profiling, we identified known REST-regulated miRNA genes, as well as previously uncharacterized REST-dependent miRNAs. Interestingly, in response to proliferation and differentiation stimuli, REST-regulated miRNAs formed distinct clusters and displayed variable expression dynamics. These results suggest that REST functions in a context-dependent manner through its target miRNAs for mediating neuronal production.
多能神经干细胞（NSCs）具有自我更新以及分化为神经元和神经胶质细胞的能力。然而，NSC命运决定背后的详细机制尚未完全清楚。最近的研究表明，细胞类型特异性转录因子与微小RNA（miRNAs）之间的相互作用很重要，因为驻留神经干/祖细胞会产生功能成熟的神经元。最近，我们证明转录抑制因子REST（RE1沉默转录因子）对于防止成年海马体中神经元过早分化和维持NSC自我更新至关重要。在此我们表明，在原代小鼠NSC培养物（一种生理相关细胞类型）中，REST对于协调不同miRNA亚群的表达是必需的。通过miRNA阵列分析，我们鉴定出了已知的REST调控的miRNA基因以及先前未表征的REST依赖性miRNAs。有趣的是，响应增殖和分化刺激，REST调控的miRNAs形成了不同的簇并表现出可变的表达动态。这些结果表明，REST通过其靶miRNAs以依赖于上下文的方式发挥作用，介导神经元的产生。
