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Cyclin O controls entry into the cell-cycle variant required for multiciliated cell differentiation
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Edité par CCSD ; Elsevier Inc -
International audience. 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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