Identification of Novel mRNA Transcripts in the Sympathetic Stellate Ganglia using RNA Sequencing

Abstract

IntroductionSympathetic hyperactivity is a key feature of human hypertension as well as animal models of disease. In the spontaneously hypertensive rat (SHR), a genetic‐based model of hypertension, dysautonomia occurs prior to increases in blood pressure.AimIn this study, we aimed to establish the genetic changes in post‐ganglionic sympathetic neurons (PGSNs) obtained from SHR rats and to confirm the presence of these transcripts in stellate ganglia from human donor patients.MethodPGSNs were obtained from 16‐week normotensive Wistar rats and age‐matched hypertensive SHR with known sympathetic hyper‐responsiveness. RNA sequencing was used to investigate the transcriptomic changes within the cardiac sympathetic stellate ganglia in disease.ResultsRNAseq data were analysed using a Salmon‐DESeq2 pipeline1,2. We observed 768 differentially expressed mRNA transcripts in SHR compared with Wistar PGSNs, using the Benjamini‐Hochberg adjusted p<0.01 level. Gene ontology (GO) analysis of the rat dataset revealed extracellular ligand‐gated ion channels (GO:0005302) to be the most over‐represented ‘molecular function’ GO group. There were 15 differentially expressed genes in SHR stellate neurons within this group; including nicotinic, purinergic, glutamatergic, serotonergic, GABAergic and glycinergic receptor subunits. The presence of these transcripts was confirmed using qRT‐PCR in stellate ganglia obtained from human and rat.ConclusionRNAseq transcriptomics has revealed differential gene expression profiles in PGSNs obtained from SHR and normotensive Wistar rats. These key transcripts were also present in human stellate ganglia. Taken together, these genes require further investigation for their role in sympathetic hyperactivity and dysautonomias.Support or Funding InformationThis project was funded by the Wellcome Trust OXION initiative (105409/Z/14/Z), the British Heart Foundation, NIH SPARC (OT2OD023848) and new innovator (DP2HL142045) initiatives.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.