Of mice and humans: understanding the peripheral olfactory system
Sat-L4-001
Presented by: Anna Menini
My laboratory has been studying the molecular mechanisms involved in odorant transduction in amphibians and mice for many years. I will present some of our main findings related to proteins involved in the generation of the electrical signals produced after odorant binding to receptors in the cilia of olfactory sensory neurons in mice.
As COVID-19 affects the sense of smell in humans, we have recently turned our attention to the human olfactory epithelium. Human nasal tissues from biopsies of healthy individuals were provided by the group of Prof. Boscolo-Rizzo and Prof. Tirelli of the Section of Otolaryngology of the Department of Medical, Surgical and Health Sciences of the University of Trieste (Italy). In COVID-19, one mechanism causing cell death in some tissues is the formation of syncytia. Some studies showed that syncytia may be formed when SARS-CoV-2 Spike expressed at the surface of an infected cell binds to ACE2 on another cell, followed by activation of the scramblase TMEM16F (ANO6) which exposes phosphatidylserine to the external side of the membrane. To investigate if ACE2 and TMEM16F, the molecular components necessary for syncytia formation, are co-expressed in cells of the olfactory epithelium, we analysed a publicly available single-cell RNA-seq dataset from human nasal epithelium and performed immunohistochemistry in human nasal tissues from biopsies. We found that ACE2 and TMEM16F are co-expressed both at RNA and protein levels in non-neuronal supporting cells. We propose that one of the pathogenic mechanisms behind smell loss could be syncytia formation of supporting cells initiated by Spike binding to ACE2 and mediated by TMEM16F.
At present, my laboratory is obtaining electrophysiological recordings from supporting cells and olfactory sensory neurons of the human olfactory epithelium and I will report about these ongoing new results.
As COVID-19 affects the sense of smell in humans, we have recently turned our attention to the human olfactory epithelium. Human nasal tissues from biopsies of healthy individuals were provided by the group of Prof. Boscolo-Rizzo and Prof. Tirelli of the Section of Otolaryngology of the Department of Medical, Surgical and Health Sciences of the University of Trieste (Italy). In COVID-19, one mechanism causing cell death in some tissues is the formation of syncytia. Some studies showed that syncytia may be formed when SARS-CoV-2 Spike expressed at the surface of an infected cell binds to ACE2 on another cell, followed by activation of the scramblase TMEM16F (ANO6) which exposes phosphatidylserine to the external side of the membrane. To investigate if ACE2 and TMEM16F, the molecular components necessary for syncytia formation, are co-expressed in cells of the olfactory epithelium, we analysed a publicly available single-cell RNA-seq dataset from human nasal epithelium and performed immunohistochemistry in human nasal tissues from biopsies. We found that ACE2 and TMEM16F are co-expressed both at RNA and protein levels in non-neuronal supporting cells. We propose that one of the pathogenic mechanisms behind smell loss could be syncytia formation of supporting cells initiated by Spike binding to ACE2 and mediated by TMEM16F.
At present, my laboratory is obtaining electrophysiological recordings from supporting cells and olfactory sensory neurons of the human olfactory epithelium and I will report about these ongoing new results.