Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation.
Long noncoding RNAs in neuronal-glial fate specification and oligodendrocyte lineage maturation.
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DOI：
10.1186/1471-2202-11-14
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发表时间：
2010-02-05
期刊：
影响因子：
2.4
通讯作者：
Mehler MF
中科院分区：
文献类型：
--
作者：
Mercer TR;Qureshi IA;Gokhan S;Dinger ME;Li G;Mattick JS;Mehler MF
长链非蛋白编码 RNA (ncRNA) 正在成为细胞分化的重要调节因子，并在大脑中广泛表达。在这里，我们发现许多长 ncRNA 在神经元和少突胶质细胞 (OL) 谱系规范、神经元-胶质细胞命运转变以及 OL 谱系细化（包括髓鞘形成）的进展阶段中表现出动态表达模式。对这些动态调节的 ncRNA 的基因组背景的考虑表明，它们是包含关键神经发育蛋白编码基因的复杂转录位点的一部分，正如微阵列和原位杂交分析所示，它们表现出一致的表达谱。其中包括与分化特异性核亚结构域（如 Gomafu 和 Neat1）相关的 ncRNA，以及与发育增强子和编码重要转录因子和同源异型蛋白的基因相关的 ncRNA。我们还观察到曲古抑菌素 A 治疗后 ncRNA 表达谱的变化，曲古抑菌素 A 是一种组蛋白脱乙酰酶抑制剂，可通过改变谱系特异性基因表达程序来阻止 OL 祖细胞进展为有丝分裂后 OL。这是关于神经元和神经胶质细胞分化中长 ncRNA 表达以及通过染色质结构修饰来调节 ncRNA 表达的首次报告。这些观察结果明确地将 ncRNA 动态与神经干细胞命运决定、规范和表观遗传重编程联系起来，可能对理解和治疗神经精神疾病具有重要意义。
Long non-protein-coding RNAs (ncRNAs) are emerging as important regulators of cellular differentiation and are widely expressed in the brain. Here we show that many long ncRNAs exhibit dynamic expression patterns during neuronal and oligodendrocyte (OL) lineage specification, neuronal-glial fate transitions, and progressive stages of OL lineage elaboration including myelination. Consideration of the genomic context of these dynamically regulated ncRNAs showed they were part of complex transcriptional loci that encompass key neural developmental protein-coding genes, with which they exhibit concordant expression profiles as indicated by both microarray and in situ hybridization analyses. These included ncRNAs associated with differentiation-specific nuclear subdomains such as Gomafu and Neat1, and ncRNAs associated with developmental enhancers and genes encoding important transcription factors and homeotic proteins. We also observed changes in ncRNA expression profiles in response to treatment with trichostatin A, a histone deacetylase inhibitor that prevents the progression of OL progenitors into post-mitotic OLs by altering lineage-specific gene expression programs. This is the first report of long ncRNA expression in neuronal and glial cell differentiation and of the modulation of ncRNA expression by modification of chromatin architecture. These observations explicitly link ncRNA dynamics to neural stem cell fate decisions, specification and epigenetic reprogramming and may have important implications for understanding and treating neuropsychiatric diseases.
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