Comprehensive analysis of long noncoding RNA expression in dorsal root ganglion reveals cell-type specificity and dysregulation after nerve injury.

Comprehensive analysis of long noncoding RNA expression in dorsal root ganglion reveals cell-type specificity and dysregulation after nerve injury.
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DOI:
10.1097/j.pain.0000000000001416
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发表时间:
2019-03
期刊:
影响因子:
7.4
通讯作者:
Bennett DL
Bennett DL
中科院分区:
医学1区
文献类型:
--
作者:
Baskozos G;Dawes JM;Austin JS;Antunes-Martins A;McDermott L;Clark AJ;Trendafilova T;Lees JG;McMahon SB;Mogil JS;Orengo C;Bennett DL

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补充数字内容可在正文中找到。新的和注释的lncRNAs在神经元分化和神经损伤后表现出显著的转录变化。已鉴定的lncRNAs为反义或与疼痛基因和离子通道相邻。背根神经节(DRG)神经元提供外周组织和脊髓之间的连接。周围神经损伤后DRG感觉神经元内转录可塑性有助于神经修复,但也导致适应不良可塑性,包括神经病理性疼痛的发展。这项研究提出了已知的和新的长非编码RNA(LncRNAs)在神经损伤后的啮齿动物DRG中的组织和神经元特异性表达谱。我们已经鉴定了大量在啮齿动物DRG中表达的新的lncRNAs,其中一小部分在小鼠、大鼠和人之间是同步保守的,包括基因间和反义lncRNAs。我们还在小鼠背根神经节中发现了神经元类型特异性的lncRNAs,并在人IPS细胞来源的感觉神经元中表达了lncRNAs。我们发现在神经损伤后lncRNA的表达具有显著的可塑性,在小鼠中这一表达具有应变和性别依赖性。这一资源是公开的,将有助于未来研究DRG神经元的身份和在幼稚和受伤的DRG中的转录情况。我们介绍了我们关于新型反义和基因间lncRNA的工作,作为一个在线可搜索的数据库,可以从PainNetworks(http://www.painnetworks.org/).)访问我们还集成了PainNetworks中所有带注释的基因表达数据,因此可以在其蛋白质相互作用的背景下对它们进行检查。
Supplemental Digital Content is Available in the Text. Novel and annotated LncRNAs showed marked transcriptional change during neuron differentiation and after nerve injury. Identified LncRNAs were antisense or adjacent to pain genes and ion channels. Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and the spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron-specific expression profiling of both known and novel long noncoding RNAs (LncRNAs) in the rodent DRG after nerve injury. We have identified a large number of novel LncRNAs expressed within the rodent DRG, a minority of which were syntenically conserved between the mouse, rat, and human, and including, both intergenic and antisense LncRNAs. We have also identified neuron type–specific LncRNAs in the mouse DRG and LncRNAs that are expressed in human IPS cell–derived sensory neurons. We show significant plasticity in LncRNA expression after nerve injury, which in mice is strain and gender dependent. This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both the naive and injured DRG. We present our work regarding novel antisense and intergenic LncRNAs as an online searchable database, accessible from PainNetworks (http://www.painnetworks.org/). We have also integrated all annotated gene expression data in PainNetworks, so they can be examined in the context of their protein interactions.
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期刊: Bioinformatics (Oxford, England)
影响因子: --
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