Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation
Michella Khoury Damaa, Jacques Serizay, Rémi Balagué, Amélie-Rose Boudjema, Marion Faucourt, Nathalie Delgehyr [...] Nathalie Spassky, Alice Meunier
Authors :
Michella Khoury Damaa, Jacques Serizay, Rémi Balagué, Amélie-Rose Boudjema, Marion Faucourt, Nathalie Delgehyr, Kim Jee Goh, Hao Lu, Ee Kim Tan, Cameron T James, Catherine Faucon, Rana Mitri, Diana Carolin Bracht, Colin D Bingle, Norris Ray Dunn, Sebastian J Arnold, Laure-Emmanuelle Zaragosi, Pascal Barbry, Romain Koszul, Heymut Omran, Gabriel Gil-Gómez, Estelle Escudier, Marie Legendre, Sudipto Roy, Nathalie Spassky, Alice Meunier.
Abstract
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 G1/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.
Keywords : CP : Cell biology ; CP : Developmental biology ; Cyclin O ; PCD ; RGMC ; cell cycle ; centriole amplification ; cilia ; multiciliated cells.
Cell Rep. 2025 Jan 28 ;44(1):115117. doi : 10.1016/j.celrep.2024.115117.
