Gene expression profiling and analysis of signaling pathways involved in priming and differentiation of human neural stem cells
Gene expression profiling and analysis of signaling pathways involved in priming and differentiation of human neural stem cells
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DOI：
10.1016/j.neuroscience.2005.11.041
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Liu, M
中科院分区：
文献类型：
--
作者：
Cai, Y;Wu, P;Liu, M
人神经干细胞具有分化为CNS中所有三种主要细胞类型的能力，包括神经元、星形胶质细胞和少突胶质细胞。人类神经干细胞的多能性揭示了使用干细胞作为各种神经系统疾病的治疗工具的可能性，包括涉及功能性神经元丧失的神经退行性疾病和神经创伤。我们以前已经发现了一个启动程序，直接原代培养的人神经干细胞分化成几乎纯的神经元移植到成人中枢神经系统。然而，这种现象背后的分子机制仍然是未知的。为了揭示人神经干细胞在诱导分化过程中转录水平的变化，利用基因芯片技术研究了人神经干细胞在诱导分化过程中基因表达谱的时间变化。结果，在引发过程中，检测到520个注释基因的转录水平至少在两个时间点发生变化。此外，超过3000个假设的蛋白质编码基因和EST基因的转录水平在人神经干细胞的启动和分化过程中受到调节。我们进一步分析了命名的基因，并将它们分为14个功能类别。特别令人感兴趣的是，关键细胞信号转导途径，包括G蛋白介导的信号转导途径（异源三聚体和小单体GT3途径）、Wnt信号转导途径和TGF-β途径，通过神经干细胞引发来调节，表明这些关键信号转导途径在人神经干细胞的引发和分化中的重要作用。(c)2005年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Human neural stem cells have the ability to differentiate into all three major cell types in the CNS including neurons, astrocytes and oligodendrocytes. The multipotency of human neural stem cells shed a light on the possibility of using stem cells as a therapeutic tool for various neurological disorders including neurodegenerative diseases and neurotrauma that involve a loss of functional neurons. We have discovered previously a priming procedure to direct primarily cultured human neural stem cells to differentiate into almost pure neurons when grafted into adult CNS. However, the molecular mechanism underlying this phenomenon is still unknown. To unravel transcriptional changes of human neural stem cells upon priming, cDNA microarray was used to study temporal changes in human neural stem cell gene expression profile during priming and differentiation. As a result, transcriptional levels of 520 annotated genes were detected changed in at least at two time points during the priming process. In addition, transcription levels of more than 3000 hypothetical protein encoding genes and EST genes were modulated during the priming and differentiation processes of human neural stem cells. We further analyzed the named genes and grouped them into 14 functional categories. Of particular interest, key cell signal transduction pathways, including the G-protein-mediated signaling pathways (heterotrimeric and small monomeric GTPase pathways), the Wnt signaling pathway and the TGF-beta pathway, are modulated by the neural stem cell priming, suggesting important roles of these key signaling pathways in priming and differentiation of human neural stem cells. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.