PDF(Pubmed)
Abstract：
Diabetic peripheral neuropathy (DPN) is a common complication associated with diabetes, and can affect quality of life considerably. Dorsal root ganglion (DRG) plays an important role in the development of DPN. However, the relationship between DRG and the pathogenesis of DPN still lacks a thorough exploration. Besides, a more in-depth understanding of the cell type composition of DRG, and the roles of different cell types in mediating DPN are needed. Here we conducted single-cell RNA-seq (scRNA-seq) for DRG tissues isolated from healthy control and DPN rats. Our results demonstrated DRG includes eight cell-type populations (e.g., neurons, satellite glial cells (SGCs), Schwann cells (SCs), endothelial cells, fibroblasts). In the heterogeneity analyses of cells, six neuron sub-types, three SGC sub-types and three SC sub-types were identified, additionally, biological functions related to cell sub-types were further revealed. Cell communication analysis showed dynamic interactions between neurons, SGCs and SCs. We also found that the aberrantly expressed transcripts in sub-types of neurons, SGCs and SCs with DPN were associated with diabetic neuropathic pain, cell apoptosis, oxidative stress, etc. In conclusion, this study provides a systematic perspective of the cellular composition and interactions of DRG tissues, and suggests that neurons, SGCs and SCs play vital roles in the progression of DPN. Our data may provide a valuable resource for future studies regarding the pathophysiological effect of particular cell type in DPN.
摘要：
糖尿病周围神经病变（DPN）是与糖尿病相关的常见并发症，会严重影响生活质量。背根神经节(DRG)在DPN的发生发展中起重要作用。然而,DRG与DPN发病机制的关系尚缺乏深入的探讨。此外,更深入地了解DRG的细胞类型组成，需要不同细胞类型在介导DPN中的作用。在这里，我们对从健康对照和DPN大鼠分离的DRG组织进行了单细胞RNA-seq（scRNA-seq）。我们的结果表明DRG包括八个细胞型群体(例如，神经元，卫星胶质细胞（SGC），雪旺氏细胞（SCs），内皮细胞，成纤维细胞）。在细胞的异质性分析中，六种神经元亚型，确定了三种SGC亚型和三种SC亚型，此外，进一步揭示了与细胞亚型相关的生物学功能。细胞通讯分析显示神经元之间的动态相互作用，SGC和SC。我们还发现在神经元亚型中异常表达的转录本，SGC和SCs伴DPN与糖尿病神经性疼痛相关，细胞凋亡，氧化应激，等。总之,这项研究提供了DRG组织的细胞组成和相互作用的系统观点，并表明神经元，SGC和SCs在DPN的进展中起着至关重要的作用。我们的数据可能为有关DPN中特定细胞类型的病理生理作用的未来研究提供宝贵的资源。
