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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神经损伤后雄性和雌性小鼠感觉神经元亚型的深度 RNA-seq

DOI:
10.1101/2022.11.21.516781
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发表时间:
2022
期刊:
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影响因子:
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通讯作者:
Barry A
Barry A
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作者:
Barry A

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背根神经节(DRG)神经元在驱动急性和慢性疼痛中的作用已得到充分描述。虽然已知神经损伤会导致转录失调,但这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,同时考虑性别。我们已经利用目前可用的转基因标记荧光激活细胞分选和随后的转录组学分析的许多亚群。使用大量组织样本,我们能够规避单细胞数据集所见的低转录覆盖率和脱落率的问题。这增加了我们检测神经元亚型内基因表达的新的甚至微妙的变化的能力,并在神经元亚型水平上讨论性二态性。我们已将此资源整理成其他研究人员可访问的数据库(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定型和独特的亚型特征。虽然所有群体都有助于一般损伤特征,但也可以看到亚型富集变化。在人群中,性别和损伤之间没有很强的交叉点,但在幼稚状态下,特别是在Ab-RA 1 Ad-低阈值机械感受器中,以前未知的性别差异仍然导致损伤神经元的差异。
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 naıve states—particularly in Ab-RA 1 Ad-low threshold mechanoreceptors—still contribute to differences in injured neurons.
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