title: Single Cell Dynamics Causes Pareto-Like Effect in Stimulated T Cell Populations.
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.
authors.affiliation: Genethon, 1bis rue de l'Internationale, 91000 Evry, France.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Cosette
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France.|Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Moussy
authors.affiliation: Genethon, 1bis rue de l'Internationale, 91000 Evry, France.|Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Onodi
authors.affiliation: Genethon, 1bis rue de l'Internationale, 91000 Evry, France.|Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.
authors.forename: Adrien
authors.initials: A
authors.lastname: Auffret-Cariou
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France.|Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.
authors.forename: Thi My Anh
authors.initials: TM
authors.lastname: Neildez-Nguyen
authors.affiliation: Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.|Ecole Pratique des Hautes Etudes, Paris, France.
authors.forename: Andras
authors.initials: A
authors.lastname: Paldi
authors.affiliation: Ecole Pratique des Hautes Etudes, Paris, France.|Unit INSERM INTEGRARE UMRS 951-UEVE-EPHE, 91000 Evry, France.|Genethon, 1bis rue de l'Internationale, 91000 Evry, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Stockholm
mesh_terms: D000465:Algorithms; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003198:Computer Simulation; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000378:metabolism*