RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro
RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro
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DOI：
10.1002/jnr.23572
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发表时间：
2015-08-01
影响因子：
4.2
通讯作者：
Cacci, Emanuele
中科院分区：
文献类型：
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作者：
Soldati, Chiara;Caramanica, Pasquale;Cacci, Emanuele
成体神经干细胞（aNSC）的活性通过转录因子的募集由外部刺激调节。本研究探讨了RE 1沉默转录因子（REST）在神经干/祖细胞从成年小鼠脑室下区分离，并提供了第一个广泛的表征REST介导的控制的细胞和分子特性。这项研究表明，REST敲低影响祖细胞产生神经球的能力，减少细胞增殖，并触发细胞分化，尽管存在生长因子。全基因组和转录组分析表明，REST结合位点在与突触传递和神经系统发育和功能相关的基因中显著富集。为了寻找aNSC功能的候选调节因子，本研究鉴定了骨形态发生蛋白（BMP）家族的一个成员BMP 6，其mRNA和蛋白质在REST敲低后增加。这项研究的结果扩展了以前的研究结果，证明了骨形态发生蛋白对REST表达的相互控制。施用外源性BMP 6抑制aNSC增殖并诱导星形胶质细胞标志物胶质细胞酸性蛋白的表达，突出了其抗有丝分裂和促分化作用。这项研究表明，BMP 6与其他信号一起以REST调节的方式产生，有助于调节NSC的维持和命运。(c)2015 Wiley Periodicals，Inc.
Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. (c) 2015 Wiley Periodicals, Inc.