Deep RNA-seq of male and female murine sensory neuron subtypes after nerve injury.

Deep RNA-seq of male and female murine sensory neuron subtypes after nerve injury.
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DOI:
10.1097/j.pain.0000000000002934
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发表时间:
2023-10-01
期刊:
影响因子:
7.4
通讯作者:
--
中科院分区:
医学1区
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--
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文本中提供了补充数字内容。利用性别、损伤和时间因素,对通过荧光激活细胞分选分离的背根神经节亚型进行 RNA 测序。我们对此进行了分析和整理,作为其他人的资源。背根神经节 (DRG) 神经元在驱动急性和慢性疼痛中的作用已被充分描述。尽管已知神经损伤会导致转录失调,但这种情况在神经元亚型之间有何不同以及性别的影响尚不清楚。在这里,我们研究了多个小鼠 DRG 群体在早期和晚期疼痛状态下的深层转录谱,同时考虑了性别。我们利用目前可用的转基因技术来标记许多亚群,用于荧光激活细胞分选和随后的转录组分析。使用大量组织样本,我们能够避免单细胞数据集中转录本覆盖率低和丢失的问题。这增强了我们检测神经元亚型内基因表达的新颖甚至微妙变化的能力,并在神经元亚型水平上讨论性别二态性。我们已将此资源整理为可供其他研究人员访问的数据库(https://livedataoxford.shinyapps.io/drg-directory/)。我们在神经损伤后的早期和晚期时间点都看到了损伤状态下的刻板和独特的亚型特征。尽管所有人群都会产生一般损伤特征,但也可以看到亚型富集变化。在人群中,性别和损伤之间并没有很强的交叉点,但之前未知的幼稚状态下的性别差异——特别是在 Aβ-RA + Aδ-低阈值机械感受器中——仍然导致受伤神经元的差异。
Supplemental Digital Content is Available in the Text. Using sex, injury, and time factors, RNA-seq was performed on dorsal root ganglia subtypes isolated through fluorescent activated cell sorting. This was analyzed and curated as a resource for others. Dorsal root ganglia (DRG) neurons have been well described for their role in driving both acute and chronic pain. Although nerve injury is known to cause transcriptional dysregulation, how this differs across neuronal subtypes and the impact of sex is unclear. Here, we study the deep transcriptional profiles of multiple murine DRG populations in early and late pain states while considering sex. We have exploited currently available transgenics to label numerous subpopulations for fluorescent-activated cell sorting and subsequent transcriptomic analysis. Using bulk tissue samples, we are able to circumvent the issues of low transcript coverage and drop-outs seen with single-cell data sets. This increases our power to detect novel and even subtle changes in gene expression within neuronal subtypes and discuss sexual dimorphism at the neuronal subtype level. We have curated this resource into an accessible database for other researchers (https://livedataoxford.shinyapps.io/drg-directory/). We see both stereotyped and unique subtype signatures in injured states after nerve injury at both an early and late timepoint. Although all populations contribute to a general injury signature, subtype enrichment changes can also be seen. Within populations, there is not a strong intersection of sex and injury, but previously unknown sex differences in naïve states—particularly in Aβ-RA + Aδ-low threshold mechanoreceptors—still contribute to differences in injured neurons.
DOI: 10.1093/bioinformatics/btw313
发表时间: 2016-09-15
期刊: BIOINFORMATICS
影响因子: 5.8
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Gu, Zuguang;Eils, Roland;Schlesner, Matthias
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DOI: 10.1523/jneurosci.4569-09.2009
发表时间: 2009-11-18
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子: --
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Costigan M;Moss A;Latremoliere A;Johnston C;Verma-Gandhu M;Herbert TA;Barrett L;Brenner GJ;Vardeh D;Woolf CJ;Fitzgerald M
通讯作者: Fitzgerald M