Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain
Persistent Alterations in Microglial Enhancers in a Model of Chronic Pain
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DOI：
10.1016/j.celrep.2016.04.063
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发表时间：
2016-05-24
期刊：
影响因子：
8.8
通讯作者：
McMahon, Stephen B.
中科院分区：
文献类型：
--
作者：
Denk, Franziska;Crow, Megan;McMahon, Stephen B.
慢性疼痛是一种常见且具有破坏性的疾病，可诱导神经元和小胶质细胞发生明显的变化。一个主要的未解决的问题是，为什么这些变化在诱发性损伤愈合后还会持续很长时间。在这里，我们认为神经损伤的一些更持久的后果可能隐藏在表观基因组中。细胞分选和测序技术用于表征慢性神经性疼痛小鼠模型的脊髓免疫反应。外周髓细胞浸润缺失，中枢小胶质细胞RNA测序（RNA-seq）显示神经结扎后基因表达发生短暂变化。相反，对小胶质细胞增强剂的检查显示，在接近转录调节基因的地方，损伤后发生了持续的改变。增强子是定义细胞转录因子结合谱的开放染色质区域。我们假设增强子的变化可能构成了一种在分子水平上记录痛苦经历的机制。
Chronic pain is a common and devastating condition that induces well-characterized changes in neurons and microglia. One major unanswered question is why these changes should persist long after the precipitating injury has healed. Here, we suggest that some of the longer-lasting consequences of nerve injury may be hidden in the epigenome. Cell sorting and sequencing techniques were used to characterize the spinal cord immune response in a mouse model of chronic neuropathic pain. Infiltration of peripheral myeloid cells was found to be absent, and RNA sequencing (RNA-seq) of central microglia revealed transient gene expression changes in response to nerve ligation. Conversely, examination of microglial enhancers revealed persistent, post-injury alterations in close proximity to transcriptionally regulated genes. Enhancers are regions of open chromatin that define a cell's transcription factor binding profile. We hypothesize that changes at enhancers may constitute a mechanism by which painful experiences are recorded at a molecular level.