Serizay Jacques, Khoury Damaa Michella, Boudjema Amélie-Rose, Balagué Rémi, Faucourt Marion, Delgehyr Nathalie, Noûs Camille, Zaragosi Laure-Emmanuelle, Barbry Pascal, Spassky Nathalie, Koszul Romain, Meunier Alice
Institut de Biologie de l'ENS (IBENS), CNRS, INSERM, École Normale Supérieure, PSL Research University, Paris, France; Institut Pasteur, CNRS UMR3525, Université Paris Cité, Unité Régulation Spatiale des Génomes, Paris, France.
Institut de Biologie de l'ENS (IBENS), CNRS, INSERM, École Normale Supérieure, PSL Research University, Paris, France.
Cell Rep. 2025 Jan 28;44(1):115103. doi: 10.1016/j.celrep.2024.115103. Epub 2024 Dec 30.
Meiosis, endoreplication, and asynthetic fissions are variations of the canonical cell cycle where either replication or mitotic divisions are muted. Here, we identify a cell cycle variantconserved across organs and mammals, where both replication and mitosis are muted, and that orchestrates the differentiation of post-mitotic progenitors into multiciliated cells (MCCs). MCC progenitors reactivate most of the cell cycle transcriptional program but replace the temporal expression of cyclins E2 and A2 with non-canonical cyclins O and A1. In addition, the primary APC/C inhibitor Emi1 is silenced. Re-expressing cyclins E2 and A2 and/or Emi1 can induce partial replication or mitosis. This shows that a cell can co-opt the cell cycle genetic program and regulate only certain elements to qualitatively and quantitatively divert CDK activity toward differentiation rather than division. We propose this cell cycle variant to exploit the existence of a cytoplasmic-or centriolar-CDK threshold lower than the S-phase threshold.
减数分裂、核内复制和无丝分裂是典型细胞周期的变体，其中复制或有丝分裂被抑制。在此，我们鉴定出一种在器官和哺乳动物中保守的细胞周期变体，其中复制和有丝分裂均被抑制，并且该变体协调有丝分裂后祖细胞向多纤毛细胞（MCC）的分化。MCC祖细胞重新激活大部分细胞周期转录程序，但用非经典细胞周期蛋白O和A1取代细胞周期蛋白E2和A2的时序表达。此外，主要的后期促进复合物/细胞周期体（APC/C）抑制剂Emi1被沉默。重新表达细胞周期蛋白E2和A2和/或Emi1可诱导部分复制或有丝分裂。这表明细胞可以利用细胞周期遗传程序并仅调节某些元件，以定性和定量地将细胞周期蛋白依赖性激酶（CDK）活性导向分化而非分裂。我们提出这种细胞周期变体利用了低于S期阈值的细胞质或中心粒CDK阈值的存在。
