Specific microRNAs modulate embryonic stem cell-derived neurogenesis
Specific microRNAs modulate embryonic stem cell-derived neurogenesis
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DOI：
10.1634/stemcells.2005-0441
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发表时间：
2006-04-01
期刊：
影响因子：
5.2
通讯作者：
Kosik, Kenneth S.
中科院分区：
文献类型：
--
作者：
Krichevsky, Anna M.;Sonntag, Kai-C.;Kosik, Kenneth S.
微小RNA（microRNAs，miRNAs）是近年来发现的一类非编码小分子转录物，具有广泛的功能，主要存在于无脊椎动物中。作为基因表达的转录后调节因子，miRNA触发靶mRNA降解或翻译抑制。尽管已经从各种哺乳动物组织和细胞中克隆了数百种miRNAs，并预测了多种mRNA靶点，但对其功能知之甚少。到目前为止，仅描述了miRNA在造血、脂肪细胞和肌肉分化中的作用;调节胰岛素分泌;以及潜在地调节癌症生长。在这里，我们描述了在小鼠胚胎干（ES）细胞衍生的神经发生在体外的miRNA表达谱，并显示，一些miRNA的同时共诱导神经祖细胞分化为神经元和星形胶质细胞。体外ES细胞源性神经发生和体内胚胎神经发生中的miRNA表达谱之间存在明显的相关性。使用功能获得和功能丧失方法，我们证明了脑特异性miR-124 a和miR-9分子影响ES细胞衍生培养物中的神经谱系分化。此外，我们提供的证据表明，信号转导和转录激活因子（STAT）3，STAT家族通路的成员，参与这些miRNA的功能。我们的结论是，不同的miRNA发挥功能的作用，在决定神经命运的ES细胞分化。
MicroRNAs (miRNAs) are recently discovered small noncoding transcripts with a broad spectrum of functions described mostly in invertebrates. As post-transcriptional regulators of gene expression, miRNAs trigger target mRNA degradation or translational repression. Although hundreds of miRNAs have been cloned from a variety of mammalian tissues and cells and multiple mRNA targets have been predicted, little is known about their functions. So far, a role of miRNA has only been described in hematopoietic, adipocytic, and muscle differentiation; regulation of insulin secretion; and potentially regulation of cancer growth. Here, we describe miRNA expression profiling in mouse embryonic stem (ES) cell-derived neurogenesis in vitro and show that a number of miRNAs are simultaneously co-induced during differentiation of neural progenitor cells to neurons and astrocytes. There was a clear correlation between miRNA expression profiles in ES cell-derived neurogenesis in vitro and in embryonal neurogenesis in vivo. Using both gain-of-function and loss-of-function approaches, we demonstrate that brain-specific miR-124a and miR-9 molecules affect neural lineage differentiation in the ES cell-derived cultures. In addition, we provide evidence that signal transducer and activator of transcription (STAT) 3, a member of the STAT family pathway, is involved in the function of these miRNAs. We conclude that distinct miRNAs play a functional role in the determination of neural fates in ES cell differentiation.