Post-injury born oligodendrocytes incorporate into the glial scar and contribute to the inhibition of axon regeneration.-猫眼课题宝

损伤后产生的少突胶质细胞融入神经胶质疤痕并有助于抑制轴突再生。

DOI：

10.1242/dev.201311

发表时间：

2023-04-15

期刊：

Development (Cambridge, England)

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163352/

中枢神经系统投射神经元无法自发再生长距离轴突是白质病理不可逆转的基础。轴突再生研究的一个障碍是，响应实验治疗而再生的轴突在达到突触后目标之前会停止生长。在这里，我们测试了这样的假设：再生轴突与活少突胶质细胞的相互作用（在发育轴突生长过程中不存在）有助于阻碍轴突生长。为了检验这一假设，首先，我们使用单细胞 RNA 序列 (scRNA-seq) 和免疫组织学来研究视神经损伤后损伤后出生的少突胶质细胞是否融入神经胶质疤痕中。然后，我们在视神经挤压后施用诱导脱髓鞘的铜宗并通过 Pten 敲低 (KD) 刺激轴突再生。我们发现，损伤后出生的少突胶质细胞谱系细胞融入神经胶质疤痕中，在那里它们对脱髓鞘饮食敏感，从而减少了它们在神经胶质疤痕中的存在。我们进一步发现脱髓鞘饮食增强了 Pten KD 刺激的轴突再生，局部注射铜宗可促进轴突再生。我们还提供了用于比较 scRNA-seq 分析的正常和受损视神经少突胶质细胞谱系细胞的基因表达的资源。摘要：损伤后出生的少突胶质细胞融入神经胶质疤痕，有助于抑制中枢神经系统内实验刺激的轴突再生。他们还对诱导脱髓鞘的铜宗饮食敏感，这种饮食可以促进轴突再生。

Failure of central nervous system projection neurons to spontaneously regenerate long-distance axons underlies irreversibility of white matter pathologies. A barrier to axonal regenerative research is that the axons regenerating in response to experimental treatments stall growth before reaching post-synaptic targets. Here, we test the hypothesis that the interaction of regenerating axons with live oligodendrocytes, which were absent during developmental axon growth, contributes to stalling axonal growth. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistology to investigate whether post-injury born oligodendrocytes incorporate into the glial scar after optic nerve injury. Then, we administered demyelination-inducing cuprizone and stimulated axon regeneration by Pten knockdown (KD) after optic nerve crush. We found that post-injury born oligodendrocyte lineage cells incorporate into the glial scar, where they are susceptible to the demyelination diet, which reduced their presence in the glial scar. We further found that the demyelination diet enhanced Pten KD-stimulated axon regeneration and that localized cuprizone injection promoted axon regeneration. We also present a resource for comparing the gene expression of scRNA-seq-profiled normal and injured optic nerve oligodendrocyte lineage cells. Summary: Post-injury born oligodendrocytes incorporate into the glial scar and contribute to inhibiting experimentally stimulated axon regeneration within the CNS. They are also susceptible to the demyelination-inducing cuprizone diet, which promotes axon regeneration.