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 e..., Experimental design and participants
The objective of this study was to establish the causes of smell alterations observed in cystic fibrosis patients. In a prospective study design, patients who presented themselves with CF were recruited from CF outpatient clinic consultations in the sense of regular disease-specific follow-up. Healthy subjects were recruited for comparison. For the Sniffin’ Sticks test, a total of 3 healthy participants (aged 23 to 52 years, 1 woman) and 10 CF patients (aged 18-52 years, 5 women) participated in the study from 07/04/2023 to 07/25/2023. For the SNOT-22 test, 17 healthy controls (23-52 years old, 10 women) and the previous 10 CF were used. For snRNA-seq, samples from 7 CF and 9 controls were sequenced. The information on the genetic form of the disease comes from the documentation of earlier DNA tests. For healthy participants, exclusion criteria were neurological diseases, systemic diseases associated with smell disorders like chronic renal failure, s..., , # Cystic fibrosis alters the structure of the olfactory epithelium and the expression of olfactory receptors affecting odor perception

[https://doi.org/10.5061/dryad.w9ghx3g0p](https://doi.org/10.5061/dryad.w9ghx3g0p)

## Description of the data and file structure

Bulk and Single-nuclei RNA-seq data generated in this publication have been deposited in NCBI's Gene Expression Omnibus (GEO) and are accessible through GEO Series accession number GSE197187 and available in [https://www.genomique.info//data/public/hts/9258/8646_human_olfactory_cf.h5ad](https://www.genomique.info//data/public/hts/9258/8646_human_olfactory_cf.h5ad).

### **Human olfactory data**

* *Mutation*: type of *CFTR* gene mutation
* *Kaftrio*: type of cystic fibrosis treatment with kaftrio (Yes=1/No=0)
* *Age*: Age range of participants
* *m/f*: Gender/sex of participants (male=1/female=0)
* *Symptoms*: Whether participants present symptoms of cystic fibrosis (Yes=1/No=0)
* *Polyps*: Whether participants present nasal...