Matrisome Expression in the Dorsal Root Ganglion

Abstract

The extracellular matrix (ECM) is a three-dimensional network of macromolecules that provides mechanical support to cells and tissues. The ECM also plays a role in cell signaling and morphology. It comprises various proteins which are called the matrisome. It consists of a core matrisome and matrisome-associated proteins. Recently, the ECM was identified as the most regulated pathway in animal pain models. However, mechanistic insights into the role of ECM in pain are lacking. Therefore, we will examine matrisome gene expression in the peripheral nervous system, in particular in murine dorsal root ganglia (DRG). This study's goal is to investigate the cellular distribution for matrisome gene expression in the DRG. Single-cell RNA sequencing (scRNAseq) was performed on 11 pooled 18-week-old male wild-type mice L3-L5 DRGs to analyze matrisome gene expression. Samples were sequenced by 10X Genomics and analyzed with the Seurat 4.0 package in Rstudio. The DRG consist of different cell types from various neuronal cells, supporting cells, vascular cells, pericytes and immunological cells. The core matrisome (glycoproteins (83% expressed), collagens (98%) and proteoglycans (92%)) is highly expressed in the DRG (Fig1A). Collagens and proteoglycans are mainly expressed by vascular cell types, Schwann, and satellite glial cells, while glycoproteins are expressed by neuronal, vascular cell types and pericytes (Fig1B). Matrisome associated proteins had a lower coverage but were still widely expressed by DRG cells: secreted factors (68%), ECM-affiliated proteins (75%), and ECM-regulators (62%). Neuronal cell types are the dominant cell type for expression of the matrisome-associated proteins. DRG neurons express both core matrisome as well as matrisome-associated genes, supporting the idea that the matrisome may contribute to pain signaling. Identifying the cellular distribution of the matrisome genes provides a framework to study the role of the ECM in peripheral neuronal tissue and its influence on pain. Grant support from Rachel Miller: R01AR077019 Anne-Marie Malfait: R01AR064251, R01AR060364, P30AR079206 Delfien Syx:12Q5920N Fransiska Malfait: 1842318N FWO project: G041519N.