中国神经再生研究(英文版) ›› 2022, Vol. 17 ›› Issue (6): 1334-1342.doi: 10.4103/1673-5374.327360

• 原著:脊髓损伤修复保护与再生 • 上一篇    下一篇

成年斑马鱼脊髓损伤修复的关键基因

  

  • 出版日期:2022-06-15 发布日期:2021-12-17

Identification of key genes involved in recovery from spinal cord injury in adult zebrafish

Wen-Yuan Shen1, #, Xuan-Hao Fu1, #, Jun Cai2, #, Wen-Chang Li2, Bao-You Fan1, Yi-Lin Pang1, Chen-Xi Zhao1, Muhtidir Abula1, Xiao-Hong Kong3, Xue Yao1,*, Shi-Qing Feng1, *   

  1. 1International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China; 2Tianjin Medicine and Health Research Center, Tianjin Institute of Medical & Pharmaceutical Sciences, Tianjin, China; 3School of Medicine, Nankai University, Tianjin, China
  • Online:2022-06-15 Published:2021-12-17
  • Contact: Shi-Qing Feng, MD, sqfeng@tmu.edu.cn; Xue Yao, PhD, xueyao@tmu.edu.cn.
  • Supported by:
    This work was financially supported by the National Natural Science Foundation of China (No. 81972074; to XY), the National Key R&D Project (No. 2019YFA0112100; to SQF), Tianjin Key Research and Development Plan, Key Projects for Science and Technology Support (No. 19YFZCSY00660; to SQF), Tianjin Medical University General Hospital Youth Incubation Fund (No. ZYYFY2018003; to WYS). 

摘要:

斑马鱼是研究脊髓损伤后恢复机制的一种有效的脊椎动物模型。脊髓损伤后亚急性期是斑马鱼神经功能恢复的关键,它激活了组织桥接、轴突再生等功能。该实验发现,斑马鱼在脊髓损伤后亚急性期(2周)可以自发恢复44%的游泳运动能力,在此期间共鉴定出脊髓组织中的7 762个差异表达基因,其中2 950个表达上调,4 812个表达下调,这些差异表达基因的生物学过程主要集中在呼吸链、轴突再生和细胞成分形态发生等方面,主要参与代谢途径、细胞周期和基因调控途径的调控。随后实验验证了斑马鱼脊髓组织的2个差异表达基因--claps2基因表达上调和h1m基因表达下调的确切结果;在功能验证方面分析可见,脊髓损伤后上调的clasp2基因与微管结合蛋白功能类似,负责由微管调节的轴突延伸,而脊髓损伤后下调的h1m基因可能归因于脊髓损伤时其对内源性干细胞分化的调节。该研究为脊髓损伤修复提供了新的候选基因,clasp2和h1m基因是神经再生的潜在治疗干预靶点。

https://orcid.org/0000-0001-9437-7674 (Shiqing Feng); https://orcid.org/0000-0003-4904-7697 (Xue Yao)

关键词: 脊髓损伤, 内源性神经干细胞, 神经发生, clasp2, h1m, nanog, 轴突再生, 微管, 亚急性阶段, 神经再生

Abstract: Zebrafish are an effective vertebrate model to study the mechanisms underlying recovery after spinal cord injury. The subacute phase after spinal cord injury is critical to the recovery of neurological function, which involves tissue bridging and axon regeneration. In this study, we found that zebrafish spontaneously recovered 44% of their swimming ability within the subacute phase (2 weeks) after spinal cord injury. During this period, we identified 7762 differentially expressed genes in spinal cord tissue: 2950 were up-regulated and 4812 were down-regulated. These differentially expressed genes were primarily concentrated in the biological processes of the respiratory chain, axon regeneration, and cell-component morphogenesis. The genes were also mostly involved in the regulation of metabolic pathways, the cell cycle, and gene-regulation pathways. We verified the gene expression of two differentially expressed genes, clasp2 up-regulation and h1m down-regulation, in zebrafish spinal cord tissue in vitro. Pathway enrichment analysis revealed that up-regulated clasp2 functions similarly to microtubule-associated protein, which is responsible for axon extension regulated by microtubules. Down-regulated h1m controls endogenous stem cell differentiation after spinal cord injury. This study provides new candidate genes, clasp2 and h1m, as potential therapeutic intervention targets for spinal cord injury repair by neuroregeneration. All experimental procedures and protocols were approved by the Animal Ethics Committee of Tianjin Institute of Medical & Pharmaceutical Sciences (approval No. IMPS-EAEP-Q-2019-02) on September 24, 2019. 

Key words: axon regeneration, clasp2, endogenous neural stem cells, h1m, microtubule, nanog, neural regeneration, neurogenesis, spinal cord injury, subacute phase

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