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Quantifying cellular dynamics in mice using a novel fluorescent division reporter system.

Eva Lukas1,2, Thea Hogan3, Cayman Williams3

  • 1Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY, United States.

Frontiers in Immunology
|August 14, 2023
PubMed
Summary
This summary is machine-generated.

This study introduces a novel Ki67 reporter mouse system for tracking cell dynamics. This method accurately measures T cell lifespans and division rates, offering a promising alternative for cellular dynamics research.

Keywords:
dynamicsimmunologymathematical modelmouse modelnaive T cells

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Area of Science:

  • Immunology
  • Cell Biology
  • Systems Biology

Background:

  • Cell population dynamics are crucial for understanding immune responses and tissue homeostasis.
  • Traditional methods like pulse-chase DNA labeling combined with mathematical modeling estimate cell production and turnover rates.
  • Existing techniques face challenges in providing unbiased parameter estimates and comprehensive uncertainty measures.

Purpose of the Study:

  • To introduce and validate a novel cell fate-mapping mouse model utilizing a Ki67 reporter construct for quantifying cellular dynamics.
  • To measure the lifespans and division rates of naive CD4 and CD8 T cells using this reporter system.
  • To propose an improved modeling approach for unbiased parameter estimation in cellular dynamics.

Main Methods:

  • Development and utilization of a Ki67 reporter mouse model for constitutive fluorescent protein expression in dividing cells.
  • Application of a pulse-chase approach with the reporter mouse system to track cell populations.
  • Employing various mathematical modeling strategies to analyze labeled cell frequencies over time.

Main Results:

  • The Ki67 reporter mouse system successfully measured lifespans and division rates of naive CD4 and CD8 T cells.
  • Estimates derived from this system were consistent with those obtained from established methods.
  • Simultaneous modeling of labeled cell frequencies in the population of interest and its precursor is proposed for unbiased estimates.

Conclusions:

  • Ki67 reporter mice represent a promising and effective system for studying cellular dynamics.
  • The proposed simultaneous modeling approach enhances the accuracy and reliability of parameter estimation.
  • This methodology offers a valuable tool for advancing research in immunology and cell biology.