Zhang Ruirui, Chen Sailing, Wang Xinghui, Gu Xiaosong, Yi Sheng
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, China.
Glia. 2021 Mar;69(3):765-778. doi: 10.1002/glia.23928. Epub 2020 Oct 20.
Peripheral nerves connect central nerves with target tissues and organs and execute vital signal transduction functions. Although sub-types of neurons have been defined, the heterogeneity of cell populations in peripheral nerves, especially Schwann cells, has not been well demonstrated. Here, we collected sciatic nerves (SN) and dorsal root ganglia (DRG) from neonatal (1-day old) rats and classified cell populations by high-coverage single-cell sequencing. A total of 10 types of cells, including endothelial cells, erythrocytes, fibroblasts, monocytic cells, neurons, neutrophils, pericytes, satellite cells, Schwann cells, and vascular smooth muscle cells, were identified by transcriptome-based cell typing. The comparisons of cells in neonatal rat SN and DRG revealed distinct atlas in different tissue localizations. Investigations of ligand-receptor interactions showed that there existed direct cell-cell communications between endothelial cells and fibroblasts in SN and among endothelial cells, fibroblasts, and vascular smooth muscle cells in DRG. Schwann cells in neonatal rats were further sub-grouped to four sub-types, including LOC100134871 and Hbb expressing Schwann cell sub-type 1, Cldn19 and Emid1 expressing Schwann cell sub-type 2, Timp3 and Col5a3 expressing Schwann cell sub-type 3, and Cenpf and Mki67 expressing Schwann cell sub-type 4. These Schwann cell sub-types exhibited distinct genetic features and functional enrichments. Collectively, our results illustrated the diversity and cellular complexity of peripheral nerves at the neonatal stage and revealed the heterogeneity of Schwann cells in the peripheral nervous system.
外周神经将中枢神经与靶组织和器官相连，并执行重要的信号转导功能。尽管神经元的亚型已被定义，但外周神经中细胞群体的异质性，尤其是雪旺细胞的异质性，尚未得到充分证明。在这里，我们从新生（1日龄）大鼠中收集坐骨神经（SN）和背根神经节（DRG），并通过高覆盖度单细胞测序对细胞群体进行分类。通过基于转录组的细胞分型，共鉴定出10种细胞类型，包括内皮细胞、红细胞、成纤维细胞、单核细胞、神经元、中性粒细胞、周细胞、卫星细胞、雪旺细胞和血管平滑肌细胞。新生大鼠SN和DRG中细胞的比较揭示了不同组织定位中的独特图谱。配体-受体相互作用的研究表明，SN中的内皮细胞和成纤维细胞之间以及DRG中的内皮细胞、成纤维细胞和血管平滑肌细胞之间存在直接的细胞间通讯。新生大鼠的雪旺细胞进一步细分为四个亚型，包括表达LOC100134871和Hbb的雪旺细胞亚型1、表达Cldn19和Emid1的雪旺细胞亚型2、表达Timp3和Col5a3的雪旺细胞亚型3以及表达Cenpf和Mki67的雪旺细胞亚型4。这些雪旺细胞亚型表现出独特的遗传特征和功能富集。总的来说，我们的结果说明了新生期外周神经的多样性和细胞复杂性，并揭示了外周神经系统中雪旺细胞的异质性。
