Project description:While the inflammatory immune response of the lung to allergens and pathogens has been extensively studied, little is known about how sensory nerves change in response to an inflammatory insult within the organ they innervate. In our study we describe the collection of vagal sensory neurons innervating the mouse lung, labelled with a retrograde fluorescent tracer instilled into the airways, and the analysis of their transcriptomes by RNAseq. We also determined transcriptomes of the complete sensory ganglia (vagal, trigeminal, DRG) for comparison. We identified transcripts of genes exclusively expressed in vagal nerves, and not in any other sensory nerve type or any other organ. These include unique ion channels, G-protein coupled receptors and several transcripts of unknown function.
Project description:While the inflammatory immune response of the lung to allergens and pathogens has been extensively studied, little is known about how sensory nerves change in response to an inflammatory insult within the organ they innervate. In our study we describe the collection of vagal sensory neurons innervating the mouse lung, labelled with a retrograde fluorescent tracer instilled into the airways, and the analysis of their transcriptomes by RNAseq. We also determined transcriptomes of the complete sensory ganglia (vagal, trigeminal, DRG) for comparison. We identified transcripts of genes exclusively expressed in vagal nerves, and not in any other sensory nerve type or any other organ. These include unique ion channels, G-protein coupled receptors and several transcripts of unknown function.
Project description:While the inflammatory immune response of the lung to allergens and pathogens has been extensively studied, little is known about how sensory nerves change in response to an inflammatory insult within the organ they innervate. In our study we describe the collection of vagal sensory neurons innervating the mouse lung, labelled with a retrograde fluorescent tracer instilled into the airways, and the analysis of their transcriptomes by RNAseq. We also determined transcriptomes of the complete sensory ganglia (vagal, trigeminal, DRG) for comparison. We identified transcripts of genes exclusively expressed in vagal nerves, and not in any other sensory nerve type or any other organ. These include unique ion channels, G-protein coupled receptors and several transcripts of unknown function.
Project description:Mammalian airways and lungs are richly innervated by bronchopulmonary sensory neurons, the vast majority of which are derived from the vagal sensory ganglia. In the present study we set out to perform high coverage single cell RNA sequencing on a population of identified murine bronchopulmonary sensory neurons collected from the vagal sensory ganglia to better define the molecular expression profiles of these cell types. Given the importance of P2X2 in differentiating nodose from jugular sensory neurons, we further aimed to investigate the relationship between transcriptional expression of identified genes and P2X2 expression.
Project description:We report that molecularly distinct populations of vagal sensory neurons would play a role in causing differences in metabolic homeostasis between the sexes.
Project description:Influenza A virus (IAV) is rapidly detected in the airways by the immune system, with resident parenchymal cells and leukocytes orchestrating viral sensing and the induction of antiviral inflammatory responses. The airways are innervated by heterogenous populations of vagal sensory neurons which also play an important role in pulmonary defense. How these neurons respond to IAV respiratory infection remains unclear. Here, we use a murine model to provide the first evidence that vagal sensory neurons undergo significant transcriptional changes following a respiratory IAV infection. RNA sequencing on vagal sensory ganglia showed that IAV infection induced the expression of many genes associated with an antiviral and pro-inflammatory response
Project description:Energy homeostasis requires precise measurement of the quantity and quality of ingested food. The vagus nerve innervates the gut and can detect diverse interoceptive cues, but the identity of the key sensory neurons and corresponding signals that regulate food intake remains unknown. Here we use an approach for target-specific, single-cell RNA sequencing to generate a map of the vagal cell types that innervate the gastrointestinal tract. We show that unique molecular markers identify vagal neurons with distinct innervation patterns, sensory endings, and function. Surprisingly, we find that food intake is most sensitive to stimulation of mechanoreceptors in the intestine, whereas nutrient-activated mucosal afferents have no effect. Peripheral manipulations combined with central recordings reveal that intestinal mechanoreceptors, but not other cell types, potently and durably inhibit hunger-promoting AgRP neurons in the hypothalamus. These findings identify a key role for intestinal mechanoreceptors in the regulation of feeding.