Exploring the Single-Cell Dynamics of FOXM1 Under Cell Cycle Perturbations

Area of Science:

• Cell Biology
• Molecular Biology
• Cancer Research

Background:

• The cell cycle is vital for normal cellular function and preventing errors.
• FOXM1, a critical transcription factor, regulates cell cycle progression and is linked to various cancers.
• Limited understanding exists regarding FOXM1 dynamics during cell cycle perturbations and its role in cell fate decisions.

Purpose of the Study:

• To investigate the behavior of FOXM1 in individual cells subjected to different cell cycle perturbagens.
• To elucidate the connection between heterogeneous FOXM1 dynamics and diverse cellular fate decisions.
• To understand how FOXM1 dynamics influence cellular responses to various stimuli.

Main Methods:

• Single-cell analysis of FOXM1 dynamics.
• Exposure of cells to various perturbagens, including PLK1, CDK1, CDK1/2, and Aurora kinase inhibitors.
• Observation and classification of cellular phenotypes.

Main Results:

• Different drugs induced diverse cellular responses, attributed to heterogeneous FOXM1 dynamics at the single-cell level.
• Six distinct cellular phenotypes were identified: on-time cytokinesis, cytokinesis delay, cell cycle delay, G1 arrest, G2 arrest, and cell death.
• Inhibitor treatments targeting PLK1, CDK1, CDK1/2, and Aurora kinases demonstrated varied FOXM1 dynamics correlating with heterogeneous cellular outcomes.

Conclusions:

• FOXM1 dynamics are essential in determining cellular outcomes and responses to stimuli.
• Heterogeneous FOXM1 dynamics play a crucial role in cell cycle fate decisions, particularly under perturbation.
• This study provides insights into the mechanisms by which FOXM1 influences cell cycle progression and fate.