Li Mingchao, Banton Matthew C, Min Qing, Parkinson David B, Dun Xinpeng
Department of Neurology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
School of Biomedical Science, Faculty of Health, University of Plymouth, Plymouth, United Kingdom.
Front Cell Neurosci. 2021 Oct 21;15:688243. doi: 10.3389/fncel.2021.688243. eCollection 2021.
Following peripheral nerve injury, transcription factors upregulated in the distal nerve play essential roles in Schwann cell reprogramming, fibroblast activation and immune cell function to create a permissive distal nerve environment for axonal regrowth. In this report, we first analysed four microarray data sets to identify transcription factors that have at least twofold upregulation in the mouse distal nerve stump at day 3 and day 7 post-injury. Next, we compared their relative mRNA levels through the analysis of an available bulk mRNA sequencing data set at day 5 post-injury. We then investigated the expression of identified TFs in analysed single-cell RNA sequencing data sets for the distal nerve at day 3 and day 9 post-injury. These analyses identified 55 transcription factors that have at least twofold upregulation in the distal nerve following mouse sciatic nerve injury. Expression profile for the identified 55 transcription factors in cells of the distal nerve stump was further analysed on the scRNA-seq data. Transcription factor network and functional analysis were performed in Schwann cells. We also validated the expression pattern of Jun, Junb, Runx1, Runx2, and Sox2 in the mouse distal nerve stump by immunostaining. The findings from our study not only could be used to understand the function of key transcription factors in peripheral nerve regeneration but also could be used to facilitate experimental design for future studies to investigate the function of individual TFs in peripheral nerve regeneration.
周围神经损伤后，远端神经中上调的转录因子在雪旺细胞重编程、成纤维细胞激活和免疫细胞功能中发挥重要作用，为轴突再生创造有利的远端神经环境。在本报告中，我们首先分析了四个微阵列数据集，以鉴定在损伤后第3天和第7天小鼠远端神经残端中上调至少两倍的转录因子。接下来，我们通过分析损伤后第5天可用的大量mRNA测序数据集来比较它们的相对mRNA水平。然后，我们在损伤后第3天和第9天分析的远端神经单细胞RNA测序数据集中研究了已鉴定转录因子的表达。这些分析确定了55个在小鼠坐骨神经损伤后远端神经中上调至少两倍的转录因子。利用scRNA-seq数据进一步分析了已鉴定的55个转录因子在远端神经残端细胞中的表达谱。在雪旺细胞中进行了转录因子网络和功能分析。我们还通过免疫染色验证了Jun、Junb、Runx1、Runx2和Sox2在小鼠远端神经残端中的表达模式。我们的研究结果不仅可用于了解关键转录因子在周围神经再生中的功能，还可用于促进未来研究的实验设计，以研究单个转录因子在周围神经再生中的功能。
