Neural Regeneration Research ›› 2024, Vol. 19 ›› Issue (6): 1367-1374.doi: 10.4103/1673-5374.384067

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Prediction of cell-cell communication patterns of dorsal root ganglion cells: single-cell RNA sequencing data analysis

Yanna Lian1, 2, Cheng Wu1, 3, 4, Li Liu5, Xiangyao Li1, 2, 3, 4, *   

  1. 1National Health Commission and Chinese Academy of Medical Sciences Key Laboratory of Medical Neurobiology, Ministry of Education Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China; 2International Institutes of Medicine, the Fourth Affiliated Hospital of Zhejiang University School of Medicine, Yiwu, Zhejiang Province, China; 3Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Zhejiang University, Haining, Zhejiang Province, China; 4Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh, UK; 5Core Facilities of the School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
  • Online:2024-06-15 Published:2023-11-18
  • Contact: Xiangyao Li, PhD, Lixiangy@zju.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 32271042 and 31871062 (to XL).

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Abstract: Dorsal root ganglion neurons transmit peripheral somatic information to the central nervous system, and dorsal root ganglion neuron excitability affects pain perception. Dorsal root ganglion stimulation is a new approach for managing pain sensation. Knowledge of the cell-cell communication among dorsal root ganglion cells may help in the development of new pain and itch management strategies. Here, we used the single-cell RNA-sequencing (scRNA-seq) database to investigate intercellular communication networks among dorsal root ganglion cells. We collected scRNA-seq data from six samples from three studies, yielding data on a total of 17,766 cells. Based on genetic profiles, we identified satellite glial cells, Schwann cells, neurons, vascular endothelial cells, immune cells, fibroblasts, and vascular smooth muscle cells. Further analysis revealed that eight types of dorsal root ganglion neurons mediated proprioceptive, itch, touch, mechanical, heat, and cold sensations. Moreover, we predicted several distinct forms of intercellular communication among dorsal root ganglion cells, including cell-cell contact, secreted signals, extracellular matrix, and neurotransmitter-mediated signals. The data mining predicted that Mrgpra3-positive neurons robustly express the genes encoding the adenosine Adora2b (A2B) receptor and glial cell line-derived neurotrophic factor family receptor alpha 1 (GFRα-1). Our immunohistochemistry results confirmed the coexpression of the A2B receptor and GFRα-1. Intrathecal injection of the A2B receptor antagonist PSB-603 effectively prevented histamine-induced scratching behaviour in a dose-dependent manner. Our results demonstrate the involvement of the A2B receptor in the modulation of itch sensation. Furthermore, our findings provide insight into dorsal root ganglion cell-cell communication patterns and mechanisms. Our results should contribute to the development of new strategies for the regulation of dorsal root ganglion excitability.

Key words: cell-cell communications, CellChat, dorsal root ganglion, scRNA-Seq database