Snrna-Seq Maps Interplay Of Ganglionic Aging, Inflammation And Injury

To investigate neural variations-induced heterogeneity in trigeminal cellular subtypes, with a focus on the mechanisms underlying the impact of aging, peripheral inflammation and injury on the ganglion. Single-nucleus RNA sequencing was performed on trigeminal ganglia (TG) from four groups of C57BL/6 mice: (1) natural aging (20-month-old), (2) chronic pulpitis (8-10-week-old), (3) inferior alveolar nerve transection (8-10-week-old), and (4) age-matched control (8-10-week-old). Multidimensional analyses encompassing UMAP dimensionality reduction, DEA (Differential Expression Analysis), GO/KEGG pathway enrichment, Gene Set Enrichment/ Variation Analysis (GSEA/GSVA), Single-Cell Regulatory Network Inference and Clustering (SCENIC), CellChat and so on were used to demonstrate cellular alterations in TG under diverse neural variation states. Chronic pulpitis being a potential driver of TG cell senescence, in both aging and chronic inflammatory states, the TG of mice exhibited extensive similarities in cell subtype composition, differentially expressed genes (DEGs), gene functional enrichment, and cell-cell interactions. Notably, four neuronal subtypes exhibit shared susceptibility to both inflammation and aging, along with distinct glial cell and schwann cell subtypes demonstrating inflammation-associated phenotypic polarization. Following neural injury, specialized TG cell subpopulations emerge as critical regulators of both axonal regeneration and nociceptive suppression. This study reveals common susceptible cell subtype targets in the TG under inflammatory and aging conditions, as well as the mechanisms underlying sensory dysfunction and its chronicity. Furthermore, the research uncovers the intrinsic protective and reparative mechanisms of the nervous system in response to injury.