Analysis of matrisome expression patterns in murine and human dorsal root ganglia

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Fransiska Malfait¹  Zoë Malfait¹  Robin Vroman¹  Delfien Syx¹  Anne-Marie Malfait²  Rachel E. Miller²  Rahel S. Hunter²  Matthew J. Wood²  Dale S. George³  Diana Tavares-Ferreira⁴  Olivia C. Davis⁴  Theodore J. Price⁴  Richard J. Miller⁵  Dongjun Ren⁵ 

[1] Department of Biomolecular Medicine, Center for Medical Genetics, Ghent University, Ghent, Belgium;Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center, Chicago, IL, United States;Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States;Department of Neuroscience and Center for Advanced Pain Studies, University of Texas at Dallas, Richardson, TX, United States;Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States;

关键词: matrisome;    dorsal root ganglion;    nociceptor;    cell–cell communication;    extracellular matrix;   

DOI  :  10.3389/fnmol.2023.1232447

 received in 2023-05-31, accepted in 2023-07-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

The extracellular matrix (ECM) is a dynamic structure of molecules that can be divided into six different categories and are collectively called the matrisome. The ECM plays pivotal roles in physiological processes in many tissues, including the nervous system. Intriguingly, alterations in ECM molecules/pathways are associated with painful human conditions and murine pain models. Nevertheless, mechanistic insight into the interplay of normal or defective ECM and pain is largely lacking. The goal of this study was to integrate bulk, single-cell, and spatial RNA sequencing (RNAseq) datasets to investigate the expression and cellular origin of matrisome genes in male and female murine and human dorsal root ganglia (DRG). Bulk RNAseq showed that about 65% of all matrisome genes were expressed in both murine and human DRG, with proportionally more core matrisome genes (glycoproteins, collagens, and proteoglycans) expressed compared to matrisome-associated genes (ECM-affiliated genes, ECM regulators, and secreted factors). Single cell RNAseq on male murine DRG revealed the cellular origin of matrisome expression. Core matrisome genes, especially collagens, were expressed by fibroblasts whereas matrisome-associated genes were primarily expressed by neurons. Cell–cell communication network analysis with CellChat software predicted an important role for collagen signaling pathways in connecting vascular cell types and nociceptors in murine tissue, which we confirmed by analysis of spatial transcriptomic data from human DRG. RNAscope in situ hybridization and immunohistochemistry demonstrated expression of collagens in fibroblasts surrounding nociceptors in male and female human DRG. Finally, comparing human neuropathic pain samples with non-pain samples also showed differential expression of matrisome genes produced by both fibroblasts and by nociceptors. This study supports the idea that the DRG matrisome may contribute to neuronal signaling in both mouse and human, and that dysregulation of matrisome genes is associated with neuropathic pain.

【 授权许可】

Unknown   
Copyright © 2023 Vroman, Hunter, Wood, Davis, Malfait, George, Ren, Tavares-Ferreira, Price, Miller, Malfait, Malfait, Miller and Syx.