Cystic fibrosis alters the structure of the olfactory epithelium and the expression of olfactory receptors affecting odor perception

A reduced sense of smell is a common condition in people with cystic
fibrosis (CF) that negatively impacts their quality of life. While often
attributed to nasal mucosa inflammation, the underlying causes of the
olfactory loss remain unknown. Here, we characterized gene expression in
olfactory epithelium cells from CF patients using single-nuclei RNA
sequencing and found altered expression of olfactory receptors (ORs) and
genes related to progenitor cell proliferation. We confirmed these
findings in newborn, inflammation-free samples of a CF animal model, and
further identified ultrastructural alterations in the olfactory epithelium
and bulbs of these animals. We established that CFTR, the anion channel
whose dysfunction causes CF, is dispensable for odor-evoked signaling in
sensory neurons, yet CF animals displayed defective odor-guided behaviors
consistent with the morphological and molecular alterations. Our study
highlights CF's major role in modulating epithelial structure and OR
expression, shedding light on the mechanisms contributing to olfactory
loss in CF.