Transcriptional Profiling of Individual Airway Projecting Vagal Sensory Neurons
Bronchopulmonary sensory neurons are derived from the vagal sensory ganglia and are essential for monitoring the physical and chemical environment of the airways and lungs. Subtypes are heterogenous in their responsiveness to stimuli, phenotype, and developmental origin, but they collectively serve to regulate normal respiratory and pulmonary processes and elicit a diverse range of defensive physiological responses that protect against noxious stimuli. In this study, we aimed to investigate the transcriptional features of vagal bronchopulmonary sensory neurons using single-cell RNA sequencing (scRNA-seq) to provide a deeper insight into their molecular profiles. Retrogradely labeled vagal sensory neurons projecting to the airways and lungs were hierarchically clustered into five types reflecting their developmental lineage (neural crest versus placodal) and putative function (nociceptors versus mechanoreceptors). The purinergic receptor subunit P2rx2 is known to display restricted expression in placodal-derived nodose neurons, and we demonstrate that the gene profiles defining cells high and low in expression of P2rx2 include G protein coupled receptors and ion channels, indicative of preferential expression in nodose or jugular neurons. Our results provide valuable insight into the transcriptional characteristics of bronchopulmonary sensory neurons and provide rational targets for future physiological investigations.
KeywordsP2X2 Cough Nodose Jugular Bronchopulmonary Single-cell RNA-sequencing Vagus nerve Sensory neurons Adenosine triphosphate
The authors acknowledge Ms. Jennifer Keller for expert technical assistance in aspects of this study.
Funded by grants to S.B.M  and A.E.M  from the National Health and Medical Research Council of Australia.
Compliance with Ethical Standards
Experiments using pathogen-free C57BL/6 mice (8–10 weeks, male, n = 30) were approved by the University of Melbourne, Parkville, Australia, accredited institutional animal ethics committee in accordance with the Australian code for the care and use of animals for scientific purposes.
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