BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.

BDNF and the maturation of posttranscriptional regulatory networks in human SH-SY5Y neuroblast differentiation.
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DOI:
10.3389/fncel.2014.00325
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发表时间:
2014
影响因子:
5.3
通讯作者:
Cairns MJ
Cairns MJ
中科院分区:
医学2区
文献类型:
--
作者:
Goldie BJ;Barnett MM;Cairns MJ

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SH-SY5Y 培养系统是一种方便的神经元模型,具有阐述人类/灵长类动物特异性转录网络和与人类认知障碍相关的途径的潜力。虽然该系统允许探索人类基因组中的特殊特征,但对于如何实现该模型及其是否适合回答与人类神经结构相关的复杂功能问题仍然存在重大争论。鉴于这些问题,我们试图描述两阶段 ATRA 分化的转录后调控结构,即 Encinas 等人提出的 BDNF 成熟方案。使用综合全基因组基因和 microRNA (miRNA) 表达分析。我们报告说,与单独的 ATRA 相比,ATRA-BDNF 诱导关键突触基因、大脑特异性 miRNA 和 miRNA 生物发生机制的表达以及 AChE 活性显着增加。功能注释聚类将 BDNF 与神经元术语以及仅 ATRA 聚类中未发现的突触术语更显着相关。虽然我们的结果支持使用 SH-SY5Y 作为神经元模型,但我们主张考虑选择相对于建模系统的分化剂。
The SH-SY5Y culture system is a convenient neuronal model with the potential to elaborate human/primate-specific transcription networks and pathways related to human cognitive disorders. While this system allows for the exploration of specialized features in the human genome, there is still significant debate about how this model should be implemented, and its appropriateness for answering complex functional questions related to human neural architecture. In view of these questions we sought to characterize the posttranscriptional regulatory structure of the two-stage ATRA differentiation, BDNF maturation protocol proposed by Encinas et al. using integrative whole-genome gene and microRNA (miRNA) expression analysis. We report that ATRA-BDNF induced significant increases in expression of key synaptic genes, brain-specific miRNA and miRNA biogenesis machinery, and in AChE activity, compared with ATRA alone. Functional annotation clustering associated BDNF more significantly with neuronal terms, and with synaptic terms not found in ATRA-only clusters. While our results support use of SH-SY5Y as a neuronal model, we advocate considered selection of the differentiation agent/s relative to the system being modeled.
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