Molecular Diversity of Pulmonary Sensory Neurons Revealed by Single Cell RNA Sequencing

Pulmonary sensory neurons are primary sensory neurons that monitor lung physiological state, and communicate that information to the central nervous system. Many symptoms associated with pulmonary diseases, such as chronic cough, dyspnea (breathlessness), and airway hyperresponsiveness, are presumed to result from abnormal behaviors of these neurons. Past studies indicate that pulmonary sensory neurons are heterogeneous in their morphologies, functions and molecular identities. However, a complete understanding of their molecular and functional diversity is still lacking. Here, we perform single cell RNA sequencing (scRNA‐seq) on mouse pulmonary sensory neurons to elucidate the genome‐wide expression profile of over a hundred individual pulmonary sensory neurons. Through unbiased clustering analysis of the expression data of these neurons, we define 7 major classes of pulmonary sensory neurons. Each class expresses distinct sets of genes implicated in physiological sensing, which predict the specific sensory functions of each class. The gene expression profiles also identify specific molecular markers for each class, which we are using to elucidate their structures, map their terminal locations and receptive fields in the lung, measure their activity, identify their synaptic partners, and reveal the physiological consequences of their activation.Support or Funding InformationDamon Runyon Postdoctoral Research Fellowship (Y.L.)M.A.K. is an investigator of the Howard Hughes Medical Institute