Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations

Sci Rep. 2015 Dec 9;5:17756. doi: 10.1038/srep17756.

Abstract

Cell fate choice during the process of differentiation may obey to deterministic or stochastic rules. In order to discriminate between these two strategies we used time-lapse microscopy of individual murine CD4 + T cells that allows investigating the dynamics of proliferation and fate commitment. We observed highly heterogeneous division and death rates between individual clones resulting in a Pareto-like dominance of a few clones at the end of the experiment. Commitment to the Treg fate was monitored using the expression of a GFP reporter gene under the control of the endogenous Foxp3 promoter. All possible combinations of proliferation and differentiation were observed and resulted in exclusively GFP-, GFP+ or mixed phenotype clones of very different population sizes. We simulated the process of proliferation and differentiation using a simple mathematical model of stochastic decision-making based on the experimentally observed parameters. The simulations show that a stochastic scenario is fully compatible with the observed Pareto-like imbalance in the final population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Cells, Cultured
  • Computer Simulation
  • Mice
  • Microscopy, Fluorescence
  • Models, Biological*
  • Phenotype
  • T-Lymphocyte Subsets / metabolism*