An age-dependent branching process model for the analysis of CFSE-labeling experiments

Area of Science:

• Mathematical Biology
• Cellular Kinetics
• Immunology

Background:

• Carboxyfluorescein succinimidyl ester (CFSE)-labeling experiments are widely used to study cell proliferation and death.
• Existing mathematical models for cell kinetics in CFSE experiments have limitations.

Purpose of the Study:

• To propose and validate a novel multi-type age-dependent branching process for modeling CFSE experiments.
• To investigate the influence of cellular dependencies on cell kinetics.
• To apply the model to human CD8+ T lymphocyte proliferation.

Main Methods:

• Development of a multi-type age-dependent branching process.
• Investigation of a competing risk version of the branching process.
• Analysis of cellular dependencies affecting population expectation.
• Application to experimental data of human CD8+ T lymphocyte proliferation.

Main Results:

• The proposed branching process model effectively describes cell proliferation and death kinetics in CFSE experiments.
• The model provided accurate estimates of cell kinetics parameters.
• The competing risk model failed to capture the kinetics of CD8+ T cells, suggesting early cell fate determination.

Conclusions:

• The age-dependent branching process is a widely applicable and robust tool for analyzing CFSE-labeling experiments.
• The model offers meaningful insights into cell division and death processes.
• The findings suggest cell fate decisions occur early in the cell cycle or earlier.