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新生小鼠小胶质细胞参与无疤脊髓修复
2020-10-10 13:59

美国哈佛医学院Zhigang He小组取得一项新突破。他们发现在新生小鼠中,小胶质细胞介导了无疤脊髓修复。2020年10月7日,国际学术期刊《自然》在线发表了这一成果。

研究人员发现在新生小鼠中脊髓的挤压伤可以无疤痕愈合,从而使长突出的轴突穿过病变而生长。新生小鼠中小胶质细胞的减少会破坏该愈合过程,并使轴突的再生停滞,这表明小胶质细胞对于协调损伤反应至关重要。使用单细胞RNA测序和功能分析,研究人员发现新生小鼠的小胶质细胞被短暂激活,并且在无疤痕愈合过程中至少发挥两个关键作用。

首先,它们瞬时分泌纤连蛋白及其结合蛋白,形成细胞外基质的桥,该桥连接脊髓的切断末端。其次,新生儿(而非成年小鼠)小胶质细胞表达几种细胞外和细胞内肽酶的抑制剂,以及与消除炎症有关的其他分子。研究人员将经过肽酶抑制剂处理的新生小鼠小胶质细胞或成年小鼠小胶质细胞移植到成年小鼠的脊髓损伤中,发现这两种类型的小胶质细胞均可显著改善愈合和轴突再生。

总之,该研究结果揭示了新生小鼠脊髓损伤后无疤痕修复的细胞和分子基础,并提出了可用于促进成年哺乳动物神经系统无疤痕愈合的方法。

据介绍,哺乳动物的脊髓损伤可造成疤痕形成并伴随轴突几乎无法再生。

附:英文原文

Title: Microglia-organized scar-free spinal cord repair in neonatal mice

Author: Yi Li, Xuelian He, Riki Kawaguchi, Yu Zhang, Qing Wang, Aboozar Monavarfeshani, Zhiyun Yang, Bo Chen, Zhongju Shi, Huyan Meng, Songlin Zhou, Junjie Zhu, Anne Jacobi, Vivek Swarup, Phillip G. Popovich, Daniel H. Geschwind, Zhigang He

Issue&Volume: 2020-10-07

Abstract: Spinal cord injury in mammals is thought to trigger scar formation with little regeneration of axons1,2,3,4. Here we show that a crush injury to the spinal cord in neonatal mice leads to scar-free healing that permits the growth of long projecting axons through the lesion. Depletion of microglia in neonatal mice disrupts this healing process and stalls the regrowth of axons, suggesting that microglia are critical for orchestrating the injury response. Using single-cell RNA sequencing and functional analyses, we find that neonatal microglia are transiently activated and have at least two key roles in scar-free healing. First, they transiently secrete fibronectin and its binding proteins to form bridges of extracellular matrix that ligate the severed ends of the spinal cord. Second, neonatal—but not adult—microglia express several extracellular and intracellular peptidase inhibitors, as well as other molecules that are involved in resolving inflammation. We transplanted either neonatal microglia or adult microglia treated with peptidase inhibitors into spinal cord lesions of adult mice, and found that both types of microglia significantly improved healing and axon regrowth. Together, our results reveal the cellular and molecular basis of the nearly complete recovery of neonatal mice after spinal cord injury, and suggest strategies that could be used to facilitate scar-free healing in the adult mammalian nervous system.

DOI: 10.1038/s41586-020-2795-6

Source: https://www.nature.com/articles/s41586-020-2795-6

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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