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 affects 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 patients with CF 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.
Authors
- Isabelle Fleurot (ORCID: https://orcid.org/0000-0002-0728-251X)
- Ignacio Caballero (ORCID: https://orcid.org/0000-0002-0628-4134)
- Yvon Mbouamboua (ORCID: https://orcid.org/0000-0002-7764-829X)
- Nikolai Klymiuk (ORCID: https://orcid.org/0000-0003-3532-1659)
- Marie Couralet (ORCID: https://orcid.org/0000-0002-4581-8418)
- Susanne Weise (ORCID: https://orcid.org/0000-0001-7650-1731)
- Marta Barrera-Conde (ORCID: https://orcid.org/0000-0002-0106-0000)
- Matthieu Keller (ORCID: https://orcid.org/0000-0002-5445-7431)
- Pascal Barbry (ORCID: https://orcid.org/0000-0001-9632-6483)
- Pablo Chamero (ORCID: https://orcid.org/0000-0002-4305-1073)
- Raquel López‐Gálvez (ORCID: https://orcid.org/0000-0002-8458-4351)
- Thomas R. Hummel (ORCID: https://orcid.org/0000-0001-9713-0183)
- Patricia Robledo
- Nicolas Pons (ORCID: https://orcid.org/0000-0002-0390-457X)
- Nayima Quílez-Playán (ORCID: https://orcid.org/0000-0001-6593-8057)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Universitat Pompeu Fabra (ES)
- TUM Klinikum (DE)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- Physiologie de la Reproduction et des Comportements (FR)
- Hospital Del Mar (ES)
- Municipal Institute for Medical Research (ES)
- Infectiologie et santé publique (FR)
- Fondation Sophia Antipolis (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- University Hospital Carl Gustav Carus (DE)
- Technical University of Munich (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Science Advances
- Published
- 2025-02-28
- DOI
- https://doi.org/10.1126/sciadv.ads1568
- Citations
- 2
- Primary Topic
- Olfactory and Sensory Function Studies
- Type
- article
- Field-Weighted Citation Impact
- 2.93