Cyclin switch tailors a cell cycle variant to orchestrate multiciliogenesis
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.
Authors
- Nathalie Delgehyr (ORCID: https://orcid.org/0000-0001-9870-0475)
- Nathalie Spassky (ORCID: https://orcid.org/0000-0003-4722-6464)
- Pascal Barbry (ORCID: https://orcid.org/0000-0001-9632-6483)
- Romain Koszul (ORCID: https://orcid.org/0000-0002-3086-1173)
- Laure‐Emmanuelle Zaragosi (ORCID: https://orcid.org/0000-0001-6747-7928)
- Marion Faucourt
- Jacques Serizay (ORCID: https://orcid.org/0000-0002-4295-0624)
- Alice Meunier (ORCID: https://orcid.org/0000-0001-6131-7747)
- Amélie-Rose Boudjema
- Rémi Balagué
- Michella Khoury Damaa
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Côte d'Azur (FR)
- Université Paris Cité (FR)
- Université Paris Sciences et Lettres (FR)
- École Normale Supérieure - PSL (FR)
- Institut de Biologie de l'École Normale Supérieure (FR)
- Institut de Pharmacologie Moléculaire et Cellulaire (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-12-30
- DOI
- https://doi.org/10.1016/j.celrep.2024.115103
- Citations
- 10
- Primary Topic
- Microtubule and mitosis dynamics
- Type
- article
- Field-Weighted Citation Impact
- 3.26
Funders
- Association pour la Recherche sur le Cancer
- European Commission
- Agence Nationale de la Recherche
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- Centre National de la Recherche Scientifique