单细胞转录组测序技术在脊髓损伤研究中的应用

Application of single-cell RNA sequencing in spinal cord injury

背景:近年来,单细胞转录组测序技术在脊髓损伤的研究为创伤后中枢神经系统的细胞和分子异质性以及结构变化提供了新的见解。目的:就单细胞转录组测序技术在脊髓损伤的研究进展进行综述,更加全面、深入地阐述单细胞转录组测序技术在脊髓损伤领域的应用。方法:应用计算机系统检索PubMed、Web of Science、中国知网和万方数据库中2009-2023年出版的文献,英文检索词为“single-cell RNA sequencing,spinal cord injury,sequencing technology”;中文检索词为“单细胞转录组测序,脊髓损伤,测序技术”。排除质量较差、内容重复及不相关的文献,最终纳入57篇文献进行综述分析。结果与结论:目前,单细胞转录组测序技术在脊髓损伤的研究可归纳为以下几点:①鉴定了小胶质细胞、星形胶质细胞、少突胶质细胞、巨噬细胞、B细胞、神经元和神经干细胞等细胞亚群,并识别了这几种亚群的特异性标记基因。②小胶质细胞在脊髓损伤后保持永久活跃,通过增殖、免疫和稳态功能来协调脊髓损伤后的早期阶段。星形胶质细胞以激活的方式在脊髓损伤中发挥许多重要功能,包括维持微环境平衡、清除坏死组织、形成保护屏障以及胶质瘢痕等。巨噬细胞和小胶质细胞均在脊髓损伤后的慢性神经炎症中起重要作用。③神经干细胞和神经元亚群能够在脊髓损伤后进行自我更新,新发现的SCV^(sx2::Hoxa7:Zfhx3→lumbar)和SCV^(sx2::Hoxa10)等神经元亚群可再生到自然靶区,有利于运动功能的恢复。④发现细胞亚群的动态变化提高了研究者们对脊髓损伤病变进程的理解,并为脊髓损伤在不同时间点的治疗提供了新见解。截至目前,这些研究结果均还需要更多的基础研究和足够的临床试验来验证。在未来,单细胞转录组测序技术通过与生物信息学、计算机科学、组织工程学和临床医学等跨学科合作,有望为脊髓损伤的诊疗打开新的一扇窗户。

BACKGROUND:In recent years,the study of single-cell RNA sequencing technology in spinal cord injury has provided new insights into cellular and molecular heterogeneity as well as structural changes in the central nervous system after trauma.OBJECTIVE:To review the research progress of single-cell RNA sequencing technology in spinal cord injury,comprehensively and deeply expound the application of single-cell RNA sequencing technology in spinal cord injury.METHODS:A computerized system was used to search the articles published from 2009 to 2023 in PubMed,Web of Science,CNKI,and WanFang databases with the Chinese and English search terms of“single-cell RNA sequencing,spinal cord injury,sequencing technology.”Articles with poor quality,repetitive content,and non-relevance were excluded,and 57 articles were finally included for review and analysis.RESULTS AND CONCLUSION:At present,the research of single-cell RNA sequencing technology in spinal cord injury can be summarized as follows:(1)Cell subsets such as microglia,astrocytes,oligodendrocytes,macrophages,B cells,neurons,and neural stem cells were identified,and specific marker genes of these subsets were identified.(2)Microglia remain permanently active after spinal cord injury and coordinate the early stages after spinal cord injury through proliferation,immunity,and homeostatic function.Astrocytes play many important functions in spinal cord injury in an activated manner,including maintaining microenvironment balance,removing necrotic tissue,forming a protective barrier,and glial scars.Both macrophages and microglia play an important role in chronic neuroinflammation following spinal cord injury.(3)Neural stem cells and neuronal subsets can self-renew after spinal cord injury.Newly discovered neuronal subsets such as SCV^(sx2::Hoxa7:Zfhx3→lumbar) and SCV^(sx2:Hoxa10) can regenerate to natural targets and facilitate the recovery of motor function.(4)The discovery of dynamic changes in cell subsets improves our understanding of the course of spinal cord injury lesions and provides new insights into the treatment of spinal cord injury at different time points.Up to now,more basic research and sufficient clinical experiments are needed to validate the results of single-cell RNA sequencing in these studies.In the future,single-cell RNA sequencing technology is expected to open a new window for the diagnosis and treatment of spinal cord injury by interdisciplinary collaboration with bioinformatics,computer science,tissue engineering,and clinical medicine.