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, 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

Cell Reports44(1): 115117 28 January 2025

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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.

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Khoury Damaa M, Serizay J, Balagué R, Boudjema AR, Faucourt M, Delgehyr N, et al. Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation. Cell Reports. 2025;44(1):115117. doi:10.1016/j.celrep.2024.115117

@article{khourydamaa_cellrep_2025,
  author  = {Khoury Damaa, Michella and Serizay, Jacques and Balagué, Rémi and Boudjema, Amélie-Rose and Faucourt, Marion and Delgehyr, Nathalie and Goh, Kim Jee and Lu, Hao and Tan, Ee Kim and James, Cameron T. and Faucon, Catherine and Mitri, Rana and Bracht, Diana Carolin and Bingle, Colin D. and Dunn, Norris Ray and Arnold, Sebastian J. and Zaragosi, Laure-Emmanuelle and Barbry, Pascal and Koszul, Romain and Omran, Heymut and Gil-Gómez, Gabriel and Escudier, Estelle and Legendre, Marie and Roy, Sudipto and Spassky, Nathalie and Meunier, Alice},
  title   = {{Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation}},
  journal = {Cell Reports},
  year    = {2025},
  volume  = {44},
  number  = {1},
  pages   = {115117},
  doi     = {10.1016/j.celrep.2024.115117},
  url     = {https://doi.org/10.1016/j.celrep.2024.115117}
}

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