Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns
Comparative Transcriptomics of Rat and Axolotl After Spinal Cord Injury Dissects Differences and Similarities in Inflammatory and Matrix Remodeling Gene Expression Patterns
复制标题
DOI：
10.3389/fnins.2018.00808
复制
发表时间：
2018-11
影响因子：
4.3
通讯作者：
J. Tica;A. Didangelos
中科院分区：
文献类型：
--
作者：
J. Tica;A. Didangelos
哺乳动物脊髓损伤后，适应不良的炎症和基质沉积导致组织瘢痕形成和永久性功能丧失。相比之下，蝾螈在严重损伤后完全再生脊髓，没有疤痕。为了探索脊髓损伤后驱动组织反应的先前未被认识的分子和途径，我们对大鼠和美西螈转录组学数据集进行了4向交叉，并在两个物种脊髓损伤后第1天，第3天和第7天分离出具有相似或差异表达的共享基因。使用公共领域的计算工具和关键的差异调节基因的两个物种之间的系统范围内的差异和相似性进行了详细描述。在匹配的神经元基因（上调蝾螈，但在大鼠下调）和核酸代谢基因（下调蝾螈，但在大鼠上调）的持续差异表达，我们发现多个细胞外基质基因，在脊髓损伤后的两个物种和所有时间点（第1，3和7天）上调，表明在伤口愈合的细胞外基质重塑的重要性。此外，原型转录因子SP1，这是一贯上调大鼠，但在蝾螈不变，被预测为一个潜在的转录调节因子的经典炎症反应基因在大鼠中，其中大部分是不调节再生蝾螈。该分析提供了脊髓损伤后非再生哺乳动物和再生有尾目动物之间的广泛比较平台。为了更好地了解再生与瘢痕形成机制，重要的是要了解实验性脊髓损伤后一致的分子差异以及相似性。
Following spinal cord injury in mammals, maladaptive inflammation, and matrix deposition drive tissue scarring and permanent loss of function. In contrast, axolotls regenerate their spinal cord after severe injury fully and without scarring. To explore previously unappreciated molecules and pathways that drive tissue responses after spinal cord injury, we performed a 4-way intersection of rat and axolotl transcriptomics datasets and isolated shared genes with similar or differential expression at days 1, 3, and 7 after spinal cord injury in both species. Systems-wide differences and similarities between the two species are described in detail using public-domain computational tools and key differentially regulated genes are highlighted. Amongst persistent differential expression in matching neuronal genes (upregulated in axolotls but downregulated in rats) and nucleic acid metabolism genes (downregulated in axolotls but upregulated in rats), we found multiple extracellular matrix genes that were upregulated in both species after spinal cord injury and all time-points (days 1, 3, and 7), indicating the importance of extracellular matrix remodeling in wound healing. Moreover, the archetypal transcription factor SP1, which was consistently upregulated in rats but was unchanged in axolotls, was predicted as a potential transcriptional regulator of classic inflammatory response genes in rats most of which were not regulated in regenerating axolotls. This analysis offers an extensive comparative platform between a non-regenerating mammal and a regenerating urodele after spinal cord injury. To better understand regeneration vs. scarring mechanisms it is important to understand consistent molecular differences as well as similarities after experimental spinal cord injury.