Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation
Multiciliated cells (MCCs) ensure fluid circulation in various organs. Their differentiation is marked by the amplification of cilia-nucleating centrioles, driven by a genuine cell-cycle variant, which is characterized by wave-like expression of canonical and non-canonical cyclins such as Cyclin O (CCNO). Patients with CCNO mutations exhibit a subtype of primary ciliary dyskinesia called reduced generation of motile cilia (RGMC). Here, we show that Ccno is activated at the crossroads of the onset of MCC differentiation, the entry into the MCC cell-cycle variant, and the activation of the centriole biogenesis program. Its absence blocks the G<sub>1</sub>/S-like transition of the cell-cycle variant, interrupts the centriologenesis transcription program, and compromises the production of centrioles and cilia in mouse brain and human respiratory MCCs. Altogether, our study identifies CCNO as a core regulator of entry into the MCC cell-cycle variant and the interruption of this variant as one etiology of RGMC.
Authors
- Heymut Omran (ORCID: https://orcid.org/0000-0003-0282-6765)
- Catherine Faucon
- Kim Jee Goh
- Sebastian J. Arnold (ORCID: https://orcid.org/0000-0002-2688-9210)
- Nathalie Delgehyr (ORCID: https://orcid.org/0000-0001-9870-0475)
- Sudipto Roy (ORCID: https://orcid.org/0000-0002-6636-1429)
- Estelle Escudier (ORCID: https://orcid.org/0000-0002-1569-8072)
- Colin D. Bingle (ORCID: https://orcid.org/0000-0002-5405-6988)
- Cameron James
- Nathalie Spassky (ORCID: https://orcid.org/0000-0003-4722-6464)
- Pascal Barbry (ORCID: https://orcid.org/0000-0001-9632-6483)
- Marie Legendre (ORCID: https://orcid.org/0000-0003-2178-0846)
- Romain Koszul (ORCID: https://orcid.org/0000-0002-3086-1173)
- Laure‐Emmanuelle Zaragosi (ORCID: https://orcid.org/0000-0001-6747-7928)
- N. Ray Dunn (ORCID: https://orcid.org/0000-0002-6259-2975)
- Gabriel Gil‐Gómez (ORCID: https://orcid.org/0000-0002-9790-7308)
- Marion Faucourt
- Ee Kim Tan
- Jacques Serizay (ORCID: https://orcid.org/0000-0002-4295-0624)
- Diana Carolin Bracht
- Hao Lu (ORCID: https://orcid.org/0000-0002-3940-3283)
- Alice Meunier (ORCID: https://orcid.org/0000-0001-6131-7747)
- Amélie-Rose Boudjema
- Rémi Balagué
- Michella Khoury Damaa
- Rana Mitri
Institutions
- Agency for Science, Technology and Research (SG)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- University of Freiburg (DE)
- National University of Singapore (SG)
- Nanyang Technological University (SG)
- Université Côte d'Azur (FR)
- Université Paris Cité (FR)
- École Normale Supérieure - PSL (FR)
- Sorbonne Université (FR)
- Hôpital Armand-Trousseau (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- University Hospital Münster (DE)
- Institut de Biologie de l'École Normale Supérieure (FR)
- Hospital Del Mar (ES)
- Hôpital Intercommunal de Créteil (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
- Singapore Clinical Research Institute (SG)
- Singapore-MIT Alliance for Research and Technology (SG)
- Maladies génétiques d’expression pédiatrique
- Institute of Molecular and Cell Biology (SG)
- University of Sheffield (GB)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1016/j.celrep.2024.115117
- Citations
- 13
- Primary Topic
- Genetic and Kidney Cyst Diseases
- Type
- article
- Field-Weighted Citation Impact
- 7.15
Funders
- Association pour la Recherche sur le Cancer
- European Commission
- Agency for Science, Technology and Research
- Deutsche Forschungsgemeinschaft
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Fondation pour la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique
- Horizon 2020 Framework Programme
- Medical Research Council
- European Research Council
- National Medical Research Council
- HORIZON EUROPE European Research Council