LAUSR

Background: Progressive vagal dysfunction occurs with age and predisposes to pathologies in multiple visceral organs. The nodose ganglia (NG) comprises cell bodies of vagal afferent (sensory) neurons, which are crucial for interoception of cardiovascular, pulmonary, and gastro-intestinal function. Satellite glial cells (SGC) envelope and interact with vagal neurons, modulating their activity. With aging, viscero-sensory perception becomes impaired, which might simultaneously increase cardiovascular risk. What subpopulations of SGC are present in murine NG and if their activity and function similarly change during aging remains unknown. Therefore, we explored the transcriptomic profile of SGC in murine NG and characterized changes herein between young and old mice. We hypothesized that with aging SGC shift towards a more senescent and pro-inflammatory phenotype. Methods: Single-cell RNA sequencing (scRNAseq) was performed on NG of young (11.5 weeks) and old (16 months) mice (C57BL/6; N = 6/group). SGC (n = 4046 cells for young, n = 2789 cells for old) were identified by high expression of glial-specific transcripts, S100b and Fabp7. Distinct SGC populations were clustered based on transcriptomic similarity using dimensionality reduction and marker gene analyses were used for cell-type identification. Results: Cluster analysis was represented by t-distributed stochastic neighbor embedding and revealed five distinct transcriptomic subtypes. Marker genes analyses identified cluster 0 as immature SGCs based on increased expression of genes involved in development and cytoskeletal production such as Klf2 and Stmn2, respectively. Cluster 1 was enriched in genes involved in cholesterol syntheses (i.e. Me1 and Scd1), characteristic of mature, functional SGC. Cluster 2 on the other hand had high expression of genes involved in immune responses, such as Igtp and Gbp2. Cluster 3 was identified as ‘resident SGC’ based on their enrichment in genes associated with cell adhesion and extracellular matrix-related genes (i.e. Lum and Dcn), whereas cluster 4 showed high expression of early inflammatory markers and microglial markers, including C1qb and C1qa. Interestingly, with aging, the proportional size of these clusters shifted; whereas immature SGC from cluster 0 comprised 79% in young mice, they made up merely 46% in elderly mice. On the contrary, immune responsive SGC in cluster 2 only contributed to 1.4% of the SGC population in young mice but made up 37% of all SGC in old mice. Relative size of cluster 1,3 an 4 remained similar with aging. Conclusion: Using scRNAseq we demonstrated that aging causes a shift in SGC population in murine NG. Aging was characterized by a relative decrease in undifferentiated SGC and a relative increase in immune related SGC. A better understanding of aging-induced changes in SGC residing in NG could aid in preventing age-related autonomic dysfunction and optimizing vagal therapies targeted at elderly populations. NIH R01 HL148190 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.