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Cyclin switch tailors a cell cycle variant to orchestrate multiciliogenesis.

Jacques Serizay1, Michella Khoury Damaa2, Amélie-Rose Boudjema2

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Cell Reports
|December 31, 2024
PubMed
Summary

Researchers discovered a new cell cycle variant where replication and mitosis are silenced, guiding cell differentiation into multiciliated cells (MCCs). This involves altered cyclin expression and Emi1 silencing, diverting cell cycle activity towards differentiation.

Keywords:
APC/CCP: Cell biologyCP: Developmental biologycancercell cycle variantcentrioleciliaciliopathiescyclinsmeiosismulticiliated cellssingle-cell transcriptomics

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Mammalian Cell Cycle Regulation

Background:

  • Canonical cell cycles involve replication and mitotic divisions.
  • Variations like meiosis and endoreplication mute either replication or division.
  • Understanding cell cycle regulation is crucial for developmental processes.

Purpose of the Study:

  • Identify and characterize a novel cell cycle variant.
  • Investigate its role in the differentiation of multiciliated cells (MCCs).
  • Determine the molecular mechanisms underlying this cell cycle diversion.

Main Methods:

  • Analysis of cell cycle gene expression in differentiating MCC progenitors.
  • Manipulation of cyclin and APC/C inhibitor (Emi1) expression.
  • Assessment of replication and mitosis induction upon genetic manipulation.

Main Results:

  • A conserved cell cycle variant, with muted replication and mitosis, was identified in mammalian organs.
  • MCC progenitors utilize non-canonical cyclins O and A1, replacing cyclins E2 and A2.
  • Silencing of Emi1 and re-expression of cyclins E2/A2 or Emi1 induced partial replication or mitosis.

Conclusions:

  • Cells can adapt the cell cycle genetic program to prioritize differentiation over division.
  • Specific regulation of cyclins and inhibitors like Emi1 diverts CDK activity.
  • This variant may exploit a lower cytoplasmic/centriolar CDK threshold for differentiation.