PDF(Pubmed)
Abstract：
Traumatic spinal cord injury (SCI) is a disabling condition that affects millions of people around the world. Currently, no clinical treatment can restore spinal cord function. Comparison of molecular responses in regenerating to non-regenerating vertebrates can shed light on neural restoration. The axolotl (Ambystoma mexicanum) is an amphibian that regenerates regions of the brain or spinal cord after damage.
In this study, we compared the transcriptomes after SCI at acute (1-2 days after SCI) and sub-acute (6-7 days post-SCI) periods through the analysis of RNA-seq public datasets from axolotl and non-regenerating rodents.
Genes related to wound healing and immune responses were upregulated in axolotls, rats, and mice after SCI; however, the immune-related processes were more prevalent in rodents. In the acute phase of SCI in the axolotl, the molecular pathways and genes associated with early development were upregulated, while processes related to neuronal function were downregulated. Importantly, the downregulation of processes related to sensorial and motor functions was observed only in rodents. This analysis also revealed that genes related to pluripotency, cytoskeleton rearrangement, and transposable elements (e.g., Sox2, Krt5, and LOC100130764) were among the most upregulated in the axolotl. Finally, gene regulatory networks in axolotls revealed the early activation of genes related to neurogenesis, including Atf3/4 and Foxa2.
Immune-related processes are upregulated shortly after SCI in axolotls and rodents; however, a strong immune response is more noticeable in rodents. Genes related to early development and neurogenesis are upregulated beginning in the acute stage of SCI in axolotls, while the loss of motor and sensory functions is detected only in rodents during the sub-acute period of SCI. The approach employed in this study might be useful for designing and establishing regenerative therapies after SCI in mammals, including humans.
In this study, we compared the transcriptomes after SCI at acute (1-2 days after SCI) and sub-acute (6-7 days post-SCI) periods through the analysis of RNA-seq public datasets from axolotl and non-regenerating rodents.
Genes related to wound healing and immune responses were upregulated in axolotls, rats, and mice after SCI; however, the immune-related processes were more prevalent in rodents. In the acute phase of SCI in the axolotl, the molecular pathways and genes associated with early development were upregulated, while processes related to neuronal function were downregulated. Importantly, the downregulation of processes related to sensorial and motor functions was observed only in rodents. This analysis also revealed that genes related to pluripotency, cytoskeleton rearrangement, and transposable elements (e.g., Sox2, Krt5, and LOC100130764) were among the most upregulated in the axolotl. Finally, gene regulatory networks in axolotls revealed the early activation of genes related to neurogenesis, including Atf3/4 and Foxa2.
Immune-related processes are upregulated shortly after SCI in axolotls and rodents; however, a strong immune response is more noticeable in rodents. Genes related to early development and neurogenesis are upregulated beginning in the acute stage of SCI in axolotls, while the loss of motor and sensory functions is detected only in rodents during the sub-acute period of SCI. The approach employed in this study might be useful for designing and establishing regenerative therapies after SCI in mammals, including humans.
摘要：
背景：创伤性脊髓损伤（SCI）是一种致残疾病，影响全世界数百万人。目前,没有临床治疗方法可以恢复脊髓功能。再生与非再生脊椎动物的分子反应的比较可以阐明神经恢复。axolotl（Ambystomamexicanum）是一种两栖动物，在损伤后再生大脑或脊髓区域。
方法：在本研究中，我们通过分析来自axolotl和非再生啮齿动物的RNA-seq公开数据集,比较了SCI后急性(SCI后1-2天)和亚急性(SCI后6-7天)的转录组.
结果：与伤口愈合和免疫反应相关的基因在神经胶质细胞中上调，老鼠,和SCI后的小鼠；然而，免疫相关过程在啮齿类动物中更为普遍.在脊髓损伤的急性期，与早期发育相关的分子途径和基因被上调，而与神经元功能相关的过程被下调。重要的是,仅在啮齿动物中观察到与感觉和运动功能相关的过程的下调。这项分析还揭示了与多能性相关的基因，细胞骨架重排，和转座因子(例如，Sox2，Krt5和LOC100130764）在axolotl中表达最高。最后,轴突中的基因调控网络揭示了与神经发生相关的基因的早期激活，包括Atf3/4和Foxa2。
结论：脊髓损伤后不久，轴突和啮齿动物的免疫相关过程上调；然而，强烈的免疫反应在啮齿动物中更为明显。与早期发育和神经发生相关的基因在脊髓损伤急性期开始上调，而运动和感觉功能的丧失仅在SCI亚急性期的啮齿动物中检测到。本研究中采用的方法可能有助于设计和建立哺乳动物SCI后的再生疗法，包括人类。
方法：在本研究中，我们通过分析来自axolotl和非再生啮齿动物的RNA-seq公开数据集,比较了SCI后急性(SCI后1-2天)和亚急性(SCI后6-7天)的转录组.
结果：与伤口愈合和免疫反应相关的基因在神经胶质细胞中上调，老鼠,和SCI后的小鼠；然而，免疫相关过程在啮齿类动物中更为普遍.在脊髓损伤的急性期，与早期发育相关的分子途径和基因被上调，而与神经元功能相关的过程被下调。重要的是,仅在啮齿动物中观察到与感觉和运动功能相关的过程的下调。这项分析还揭示了与多能性相关的基因，细胞骨架重排，和转座因子(例如，Sox2，Krt5和LOC100130764）在axolotl中表达最高。最后,轴突中的基因调控网络揭示了与神经发生相关的基因的早期激活，包括Atf3/4和Foxa2。
结论：脊髓损伤后不久，轴突和啮齿动物的免疫相关过程上调；然而，强烈的免疫反应在啮齿动物中更为明显。与早期发育和神经发生相关的基因在脊髓损伤急性期开始上调，而运动和感觉功能的丧失仅在SCI亚急性期的啮齿动物中检测到。本研究中采用的方法可能有助于设计和建立哺乳动物SCI后的再生疗法，包括人类。
